Azetidinium-containing copolymers and uses thereof

ABSTRACT

The invention is related to azetidinium-containing copolymers and vinylic monomers and their uses in formation of non-silicone hydrogel coatings on silicone hydrogel contact lenses.

This application claims the benefits under 35 USC §119 (e) of U.S.provisional application No. 61/659,592 filed 14 Jun. 2012, incorporatedby reference in its entirety.

The present invention generally relates to azetidinium-containingvinylic monomers and copolymers suitable for applying a hydrogel coatingonto a silicone hydrogel contact lens in a cost-effective andtime-efficient manner. In addition, the present invention provides anophthalmic lens product.

BACKGROUND

Soft silicone hydrogel contact lenses are increasingly becoming popularbecause of their high oxygen permeability and comfort. But, a siliconehydrogel material typically has a surface, or at least some areas of itssurface, which is hydrophobic (non-wettable) and susceptible toadsorbing lipids or proteins from the ocular environment and may adhereto the eye. Thus, a silicone hydrogel contact lens will generallyrequire a surface modification.

A known approach for modifying the hydrophilicity of a relativelyhydrophobic contact lens material is through the use of a plasmatreatment, for example, commercial lenses such as Focus NIGHT & DAY™ andO2OPTIX™ (CIBA VISION), and PUREVISION™ (Bausch & Lomb) utilize thisapproach in their production processes. Advantages of a plasma coating,such as, e.g., those may be found with Focus NIGHT & DAY™, are itsdurability, relatively high hydrophilicity/wettability), and lowsusceptibility to lipid and protein deposition and adsorption. But,plasma treatment of silicone hydrogel contact lenses may not be costeffective, because the preformed contact lenses must typically be driedbefore plasma treatment and because of relative high capital investmentassociated with plasma treatment equipment.

Various other approaches are proposed and/or used for modifying thesurface hydrophilicity of a silicone hydrogel contact lens. Examples ofsuch other approaches include incorporation of wetting agents(hydrophilic polymers) into a lens formulation for making the siliconehydrogel contact lens (see, e.g., U.S. Pat. Nos. 6,367,929, 6,822,016,7,052,131, and 7,249,848); a layer-by-layer (LbL) polyionic materialdeposition technique (see, e.g., U.S. Pat. Nos. 6,451,871; 6,719,929;6,793,973; 6,884,457; 6,896,926; 6,926,965; 6,940,580; and 7,297,725,and U.S. Pat. Appl. Pub. Nos. 2007/0229758A1; 2008/0174035A1 and2008/0152800A1); crosslinking of LbL coatings on contact lenses has beenproposed in commonly-owned copending US pat. Appl. pub. Nos.2008/0226922 A1 and 2009/0186229 A1; and attachment of hydrophilicpolymers onto contact lenses according to various mechanisms (see forexample, U.S. Pat. Nos. 6,099,122, 6,436,481, 6,440,571, 6,447,920,6,465,056, 6,521,352, 6,586,038, 6,623,747, 6,730,366, 6,734,321,6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481, US Pat. Appl.Pub. Nos. 2009/0145086A1, 2009/0145091 A1, 2008/0142038A1, and2007/0122540A1). Although those techniques can be used in rendering asilicone hydrogel material wettable, there are some shortcomings inthose techniques. For example, wetting agents may impart haziness to theresultant lenses because of their incompatibility with other siliconecomponents in the lens formulation and may not provide a durablehydrophilic surface for extended wear purposes. LbL coatings may not beas durable as plasma coatings and may have relatively high densities ofsurface charges; which may interfere with contact lens cleaning anddisinfecting solutions. Crosslinked LbL coatings may have ahydrophilicity and/or wettability inferior than original LbL coatings(prior to crosslinking) and still have relative high densities ofsurface charges. In addition, they may not be cost-effective and/ortime-efficient for implementation in a mass production environment,because they typically require relatively long time and/or involvelaborious, multiple steps to obtain a hydrophilic coating.

Recently, a new cost-effective approach has been described in U.S. pat.Appl. pub. No. 2012/0026457 A1 (herein incorporated by reference in itsentirety) for applying a non-silicone hydrogel coating onto a siliconehydrogel contact lens. It is reported in the publication that apartially-crosslinked hydrophilic polymeric material derived from apolyamidoamine epichlorohydrin (PAE) and a wetting agent are used in theformation of non-silicone hydrogel coating on a contact lens. Althoughthis new approach can provide silicone hydrogel contact lenses withdurable hydrophilic coatings thereon, its applicability and advantagescan be limited by the lack of versatility and controllability in thelevels of hydrophilicity and/or reactive functional group contents ofthe partially-crosslinked hydrophilic polymeric material.

Therefore, there is still a need for reactive copolymers having desiredlevel of hydrophilicity and/or functional groups content for applying anon-silicone hydrogel coating onto a silicone hydrogel contact lens.

SUMMARY OF THE INVENTION

The invention, in the first aspect, provides an azetidinium-containingvinylic monomer.

The invention, in the second aspect, provides an azetidinium-containingcopolymer comprising azetidinium-containing monomeric units derived fromat least one azetidinium-containing vinylic monomer of the invention andmonomeric units derived from at least one vinylic monomer selected fromthe group consisting of a carboxyl-containing vinylic monomer, anamino-containing vinylic monomer, a hydrophobic vinylic monomer, andcombination thereof.

The invention, in the third aspect, provides a method for producingcoated silicone hydrogel contact lenses each having a crosslinkedhydrophilic coating thereon, the method of invention comprising thesteps of: (a) obtaining a silicone hydrogel contact lens; (b) applying aprime coating of an anchoring polymer onto the silicone hydrogel contactlens, wherein the anchoring polymer is a homopolymer or copolymer of acarboxyl-containing vinylic monomer and/or an azetidinium-containingcopolymer of the invention; and (c) heating the silicone hydrogelcontact lens in an aqueous solution in the presence of a water-solublethermally-crosslinkable hydrophilic polymeric material comprisingazetidinium, carboxyl, amino, and/or thiol groups, to and at atemperature from about 40° C. to about 140° C. for a period of timesufficient to induce intermolecular and intramolecular crosslinkingreactions between one azetidinium group and one amino or carboxyl group,thereby forming a durable non-silicone hydrogel coating on the siliconehydrogel contact lens, provided that at least one of the anchoringpolymer and the water-soluble thermally-crosslinkable hydrophilicpolymeric material comprises azetidinium groups.

The invention, in the fourth aspect, provides a method for producingsilicone hydrogel contact lenses each having a crosslinked hydrophiliccoating thereon, the method of invention comprising the steps of: (a)obtaining a silicone hydrogel contact lens from a lens-formingcomposition comprising an azetidinium-containing copolymer of theinvention; (b) heating the silicone hydrogel contact lens in an aqueoussolution in the presence of a water-soluble, thermally-crosslinkablehydrophilic polymeric material comprising azetidinium, carboxyl, amino,and/or thiol groups, to and at a temperature from about 40° C. to about140° C. for a period of time sufficient to induce intermolecular andintramolecular crosslinking reactions between one azetidinium group andone amino or carboxyl group, thereby forming a durable non-siliconehydrogel coating on the silicone hydrogel contact lens.

In the fifth aspect, the invention provides a silicone hydrogel contactlens comprising a non-silicone hydrogel coating thereon, wherein thenon-silicone hydrogel coating is obtained by thermally inducingintermolecular and intramolecular crosslinking of athermally-crosslinkable hydrophilic polymeric material which comprisesazetidinium-containing monomeric units derived from at least oneazetidinium-containing vinylic monomer, reactive monomeric units derivedfrom a vinylic monomer having an amino or carboxyl group, andhydrophilic monomeric units derived from a hydrophilic vinylic monomer,wherein the silicone hydrogel contact lens has an oxygen permeability ofat least about 40 barrers, a surface wettability characterized by awater contact angle of about 100 degrees or less, and a good coatingdurability characterized by surviving a digital rubbing test.

In the sixth aspect, the invention provides an ophthalmic product, whichcomprises a sterilized and sealed lens package, wherein the lens packagecomprises: a post-autoclave lens packaging solution and a readily-usablesilicone hydrogel contact lens immersed therein, wherein thereadily-usable silicone hydrogel contact lens comprises a crosslinkedhydrophilic coating obtained by autoclaving an original siliconehydrogel contact lens having amino groups and/or carboxyl groups onand/or near the surface of the original silicone hydrogel contact lensin a pre-autoclave packaging solution containing a water-soluble andthermally-crosslinkable hydrophilic polymeric material which comprisesfrom 0.001% to about 25% by mole of azetidinium-containing monomericunits derived from at least one azetidinium-containing vinylic monomer,wherein the hydrophilic polymeric material is covalently attached ontothe silicone hydrogel contact lens through second covalent linkages eachformed between one amino or carboxyl group on and/or near the surface ofthe silicone hydrogel contact lens and one azetidinium group of thehydrophilic polymeric material, wherein the post-autoclave packagingsolution comprises at least one buffering agent in an amount sufficientto maintain a pH of from about 6.0 to about 8.5 and an hydrolyzedproduct of the hydrophilic polymeric material and has a tonicity of fromabout 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1centipoise to about 10 centipoises.

These and other aspects of the invention will become apparent from thefollowing description of the presently preferred embodiments. Thedetailed description is merely illustrative of the invention and doesnot limit the scope of the invention, which is defined by the appendedclaims and equivalents thereof. As would be obvious to one skilled inthe art, many variations and modifications of the invention may beeffected without departing from the spirit and scope of the novelconcepts of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows polyhexamethylene biguanide (PHMB) uptakes and releases byvarious contact lenses.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well-known and commonly employed inthe art. Also, as used in the specification including the appendedclaims, reference to singular forms such as “a,” “an,” and “the” includethe plural, and reference to a particular numerical value includes atleast that particular value, unless the context clearly dictatesotherwise. “About” as used herein means that a number referred to as“about” comprises the recited number plus or minus 1-10% of that recitednumber.

A “silicone hydrogel contact lens” refers to a contact lens comprising asilicone hydrogel material. A “silicone hydrogel” refers to acrosslinked silicone-containing polymeric material which can absorb atleast 10 percent by weight of water when it is fully hydrated and isobtained by copolymerization of a polymerizable composition comprisingat least one silicone-containing vinylic monomer or at least onesilicone-containing vinylic macromer or at least one silicone-containingprepolymer having ethylenically unsaturated groups.

As used in this application, the term “hydrogel” or “hydrogel material”refers to a crosslinked polymeric material which is not water-solubleand can contains at least 10% by weight of water within its polymermatrix when fully hydrated.

As used in this application, the term “non-silicone hydrogel” refers toa hydrogel that is theoretically free of silicon.

A “vinylic monomer”, as used herein, refers to a compound that has onesole ethylenically unsaturated group and can be polymerized actinicallyor thermally.

The term “olefinically unsaturated group” or “ethylenically unsaturatedgroup” is employed herein in a broad sense and is intended to encompassany groups containing at least one >C═C< group. Exemplary ethylenicallyunsaturated groups include without limitation (meth)acryloylmethacryloyl

allyl, vinyl

styrenyl, or other C═C containing groups.

The term “(meth)acrylamide” refers to methacrylamide and/or acrylamide.

The term “(meth)acrylate” refers to methacrylate and/or acrylate.

A “hydrophilic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that iswater-soluble or can absorb at least 10 percent by weight water.

A “hydrophobic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that isinsoluble in water and can absorb less than 10 percent by weight water.

As used in this application, the term “macromer” or “prepolymer” refersto a medium and high molecular weight compound or polymer that containstwo or more ethylenically unsaturated groups. Medium and high molecularweight typically means average molecular weights greater than 700Daltons.

As used in this application, the term “crosslinker” refers to a compoundhaving at least two ethylenically unsaturated groups. A “crosslinkingagent” refers to a crosslinker having a molecular weight of about 700Daltons or less.

As used in this application, the term “polymer” means a material formedby polymerizing/crosslinking one or more monomers or macromers orprepolymers.

As used in this application, the term “molecular weight” of a polymericmaterial (including monomeric or macromeric materials) refers to theweight-average molecular weight unless otherwise specifically noted orunless testing conditions indicate otherwise.

As used in this application, the term “amino group” refers to a primaryor secondary amino group of formula —NHR′, where R′ is hydrogen or aC₁-C₂₀ unsubstituted or substituted, linear or branched alkyl group,unless otherwise specifically noted.

The term “carboxyl-containing vinylic monomer” refers to a vinyl monomerhaving a carboxyl group (—COOH).

The term “amino-containing vinylic monomer” refers to a vinyl monomerhaving an amino group.

The term “azetidinium” refers to a positively-charged, trivalent radical(or group) of

in which T₁, T₂ and T₃ are a direct bond.

The term “phosphorylcholine” refers to a zwitterionic group of

in which n is an integer of 1 to 5 and R₁, R₂ and R₃ independently ofeach other are C₁-C₈ alkyl or C₁-C₈ hydroxyalkyl.

The term “azlactone” refers to a mono-valent radical of

in which p is 0 or 1; T₄ and T₅ independently of each other is an alkylgroup having 1 to 14 carbon atoms, a cycloalkyl group having 3 to 14carbon atoms, an aryl group having 5 to 12 ring atoms, an arenyl grouphaving 6 to 26 carbon and 0 to 3 sulfur, nitrogen and/or oxygen atoms,or T₄ and T₅ taken together with the carbon to which they are joined canform a carbocyclic ring containing 5 to 8 ring atoms.

As used in this application, the term “non-reactive hydrophilic vinylicmonomer” refers to a hydrophilic vinylic monomer free of carboxyl oramino group.

The term “polysiloxane segment” refers to a bivalent radical having theformula

in which R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, independently of one another,are C₁-C₁₀ alkyl, C₁-C₄ alkyl- or C₁-C₄-alkoxy-substituted phenyl,C₁-C₁₀ fluoroalkyl, C₁-C₁₀ fluoroether, C₆-C₁₈ aryl radical,-alk-(OC₂H₄)_(n1)—OR₉ in which alk is C₁-C₆-alkylene divalent radical,R₉ is H or C₁-C₄ alkyl and n1 is an integer from 1 to 10, m1 and m2independently of each other are an integer of from 0 to 50 and (m1+m2)is from 1 to 100.

The term “water-soluble” in reference to a polymer means that thepolymer can be dissolved in water to an extent sufficient to form anaqueous solution of the polymer having a concentration of from about0.05% to about 30% by weight at room temperature (e.g., from about 22°C. to about 28° C.).

A “water contact angle” refers to an average water contact angle (i.e.,contact angles measured by Sessile Drop method), which is obtained byaveraging measurements of contact angles with at least 3 individualcontact lenses.

The term “intactness” in reference to a coating on a silicone hydrogelcontact lens is intended to describe the extent to which the contactlens can be stained by Sudan Black in a Sudan Black staining testdescribed in Example 1. Good intactness of the coating on a siliconehydrogel contact lens means that there is practically no Sudan Blackstaining of the contact lens.

The term “durability” in reference to a coating on a silicone hydrogelcontact lens is intended to describe that the coating on the siliconehydrogel contact lens can survive a digital rubbing test.

As used herein, “surviving a digital rubbing test” or “surviving adurability test” in reference to a coating on a contact lens means thatafter digitally rubbing the lens according to a procedure described inExample 1, water contact angle on the digitally rubbed lens is stillabout 100 degrees or less, preferably about 90 degrees or less, morepreferably about 80 degrees or less, most preferably about 70 degrees orless.

The intrinsic “oxygen permeability”, Dk, of a material is the rate atwhich oxygen will pass through a material. As used in this application,the term “oxygen permeability (Dk)” in reference to a hydrogel (siliconeor non-silicone) or a contact lens means a measured oxygen permeability(Dk) which is corrected for the surface resistance to oxygen flux causedby the boundary layer effect according to the procedures described inExample 1 of 2012/0026457 A1 (herein incorporated by reference in itsentirety). Oxygen permeability is conventionally expressed in units ofbarrers, where “barrer” is defined as [(cm³ oxygen)(mm)/(cm²)(sec)(mmHg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

The “ion permeability” through a lens correlates with the IonofluxDiffusion Coefficient. The Ionoflux Diffusion Coefficient, D (in unitsof [mm²/min]), is determined by applying Fick's law as follows:D=−n′/(A×dc/dx)where n′=rate of ion transport [mol/min]; A=area of lens exposed [mm²];dc=concentration difference [mol/L]; dx=thickness of lens [mm].

“Ophthalmically compatible”, as used herein, refers to a material orsurface of a material which may be in intimate contact with the ocularenvironment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.

The term “ophthalmically safe” with respect to a packaging solution forsterilizing and storing contact lenses is meant that a contact lensstored in the solution is safe for direct placement on the eye withoutrinsing after autoclave and that the solution is safe and sufficientlycomfortable for daily contact with the eye via a contact lens. Anophthalmically-safe packaging solution after autoclave has a tonicityand a pH that are compatible with the eye and is substantially free ofocularly irritating or ocularly cytotoxic materials according tointernational ISO standards and U.S. FDA regulations.

An “organic-based solution” refers to a solution which is a homogeneousmixture consisting of an organic-based solvent and one or more solutesdissolved in the organic based solvent. An organic-based coatingsolution refers to an organic-based solution containing at least onepolymeric coating material as a solute in the solution.

An “organic-based solvent” is intended to describe a solvent systemwhich consists of one or more organic solvents and optionally about 40%or less, preferably about 30% or less, more preferably about 20% orless, even more preferably about 10% or less, in particular about 5% orless by weight of water relative to the weight of the solvent system.

The invention is generally related to azetidinium-containing copolymersand their uses in forming a non-silicone hydrogel coating on a siliconehydrogel (SiHy) contact lens. An azetidinium-containing copolymer of theinvention can be tailored to have desired degrees ofhydrophilicity/hydrophobicity and/or azetidinium contents. Suchazetidinium-containing copolymers can be used as an anchoring polymerand/or an reactive hydrophilic polymer for forming a hydrogel coating,according to thermally-induced reaction mechanism involving anazetidnium group as illustrated in Scheme I

in which T₁, T₂ and T₃ independent of one another are a direct bond; X₁is —S—, —OC(═O)—, —O—, or —NR′— in which R′ is hydrogen, a C₁-C₂₀unsubstituted or substituted, linear or branched alkyl group; T₆ is apolymer chain or a C₁ to C₂₀ alkyl unsubstituted or substituted, linearor branched alkyl group. Such a reaction can be carried out convenientlyand directly in a lens package during autoclave (i.e., heating the lenspackage with the lens in a packaging solution about 118° C. to about125° C. for approximately 20-40 minutes under pressure) which is acommonly-used sterilization process in the contact lens industry.

The invention, in one aspect, provides one class ofazetidinium-containing vinylic monomers of formula (1)

in which: R″ is hydrogen or methyl; T₇ and T₈ independent of each otherare C₁ to C₁₄ alkyl group; Y₁, Y₂, and Y₃ independent of one other are alinkage selected from the group consisting of a direct bond, —O—, —NR′—,—C(O)NR′—, —NR′C(O)—, —O—C(O)NH—, —NHC(O)—O—, —NR′C(O)—NH—,—NH—C(O)NR′—, —C(O)—O—, —O—C(O)—, —NH—C(O)NH—Z₀—NH—C(O)NH—,—O—C(O)—NH—Z₀—NH—C(O)—O—, —O—C(O)—NH—Z₀—NH—C(O)—NH—, and—NH—C(O)—NH—Z₀—NH—C(O)—O—; R′ is hydrogen, a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkyl group; Z₀ is a linear or branchedC₂-C₁₂ alkylene divalent radical or a C₅-C₄₅ cycloaliphatic oraliphatic-cycloaliphatic divalent radical optionally containing thereinone or more linkages of —O—, —NR′— and —C(O)—, R′ is as defined above;Z₁, Z₂, and Z₃ independent of one other are a direct bond, a C₁-C₂₀unsubstituted or substituted, linear or branched alkylene divalentradical optionally containing therein one or more linkages of —O—,—NR′—, and —C(O)—, a C₁-C₇ alkyleneoxy C₁-C₇ alkylene divalent radical,a divalent radical of —(CH(R″)CH₂O)_(r1)—CH(R″)CH₂— in which R″ is asdefined above and r1 is an integer of 1 to 20, an unsubstitutedphenylene divalent radical, C₁-C₄ alkyl or C₁-C₄ alkoxy substitutedphenylene divalent radical or C₇-C₁₂ arakylene divalent radical, aC₅-C₄₅ cycloaliphatic or aliphatic-cycloaliphatic divalent radicaloptionally containing therein one or more linkages of —O—, —NR′—, and—C(O)—, a C₆-C₂₄ aromatic or araliphatic divalent radical, orcombinations thereof.

An azetidinium-containing vinylic monomer of the invention can beprepared according to a two-step process. In the first step, adi-alkylamine (HNT₇T₈) can react with epichlorohydrin

to form an azetidinium compound of

wherein T₇ and T₈ independent of each other are C₁ to C₁₄ alkyl group.In the second step, the resultant azetidinium compound reacts, in theabsence of a coupling agent, with an ethylenically functionalizingvinylic monomer selected from the group consisting of (meth)acrylic acidhalide (chloride, bromide, or iodide), (meth)acrylic anhydride, maleicanhydride, an epoxy-containing vinylic monomer, a C₂-C₆isocyanatoalkyl(meth)acrylate, an aziridine-containing vinylic monomer,and an azlactone-containing vinylic monomer, under well-known conditionsof coupling reactions between one hydroxyl group and one otherfunctional group (acid halide group, acid anhydride group, epoxy group,isocyanate group, azeridine group, or azlactone group). Alternatively,the resultant azetidinium compound reacts, in the presence of a couplingagent (e.g., a diisocyanate compound, a di-acid halide compound, adi-azlactone compound, or a di-epoxy compound), with an ethylenicallyfunctionalizing vinylic monomer selected from the group consisting of C₂to C₆ hydroxylalkyl(meth)acrylate, C₂ to C₆hydroxyalkyl(meth)acrylamide, allylalcohol, allylamine, amino-C₂-C₆alkyl(meth)acrylate, vinylamine, amino-C₂-C₆ alkyl(meth)acrylamide,acrylic acid, and C₁-C₄ alkylacrylic acid (e.g., methacrylicethylacrylic acid, propylacrylic acid, butylacrylic acid), underwell-known coupling-reaction conditions.

A “coupling reaction” is intended to describe any reaction between apair of matching functional groups in the presence or absence of acoupling agent to form covalent bonds or linkages under various reactionconditions well known to a person skilled in the art, such as, forexample, oxidation-reduction conditions, dehydration condensationconditions, addition conditions, substitution (or displacement)conditions, Diels-Alder reaction conditions, cationic crosslinkingconditions, ring-opening conditions, epoxy hardening conditions, andcombinations thereof. Non-limiting examples of coupling reactions undervarious reaction conditions between a pair of co-reactive functionalgroups are given below for illustrative purposes. For example, ahydroxyl group reacts with an acid chloride or bromide group or with anacid anhydride group to form an ester linkage (—C(O)—O—); a hydroxyl (orhydroxy) reacts with an isocyanate to form a urethane linkage; ahydroxyl reacts with an epoxy or aziridine to form a OH- orNH₂-containing ether linkage (—CH(OH)—CH₂—O— or —CH(NH₂)—CH₂—O—); ahydroxyl group reacts with an azlactone group in the presence of acatalyst to form an amidoalkylenecarboxy linkage(—OC(O)—(CH₂)_(p)—CT₄T₅—C(O)—NH—); an amino group reacts with aldehydegroup to form a Schiff base which may further be reduced; an amino group—NHR′ reacts with an acid chloride or bromide group or with an acidanhydride group to form an amide linkage (—CO—NR′—); an amino group—NHR′ reacts with an isocyanate group to form a urea linkage(—NR″—C(O)—NH—); an amino group —NHR′ reacts with an epoxy or aziridinegroup to form a OH— or NH₂-containing amine bond ((—CH(OH)—CH₂—NR′ or—CH(NH₂)—CH₂—NR′); an amino group —NHR′ reacts (ring-opening) with anazlactone group to form an alkylene-diamido linkage(—C(O)NR′—(CH₂)_(p)—CT₄T₅—C(O)—NH—); an amino group —NHR′ reacts with acarboxylic acid group in the presence of a coupling agent—carbodiimide(e.g., 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC),N,N′-dicyclohexylcarbodiimide (DCC),1-cylcohexyl-3-(2-morpholinoethyl)carbodiimide, diisopropylcarbodiimide, or mixtures thereof) to form an amide linkage; a carboxylgroup reacts with an epoxy group to form an ester bond.

Any suitable C₄-C₂₄ diisocyanates can be used in the invention. Examplesof preferred diisocyanates include without limitation isophoronediisocyanate, hexamethyl-1,6-diisocyanate, 4,4′-dicyclohexylmethanediisocyanate, toluene diisocyanate, 4,4′-diphenyl diisocyanate,4,4′-diphenylmethane diisocyanate, p-phenylene diisocyanate,1,4-phenylene 4,4′-diphenyl diisocyanate, 1,3-bis-(4,4′-isocyantomethyl)cyclohexane, cyclohexane diisocyanate, and combinations thereof.

Any suitable diacid halides can be used in the invention. Examples ofpreferred diacid halide include without limitations fumaryl chloride,suberoyl chloride, succinyl chloride, phthaloyl chloride, isophthaloylchloride, terephthaloyl chloride, sebacoyl chloride, adipoyl chloride,trimethyladipoyl chloride, azelaoyl chloride, dodecanedioic acidchloride, succinic chloride, glutaric chloride, oxalyl chloride, dimeracid chloride, and combinations thereof.

Any suitable di-epoxy compounds can be used in the invention. Examplesof preferred di-epoxy compounds are neopentyl glycol diglycidyl ether,1,4-butanediol diglycidyl ether, 1,6-hexanediol diglycidyl ether,glycerol diglycidyl ether, ethylene glycol diglycidyl ether, diethyleneglycol diglycidyl ether, polyethylene glycol diglycidyl ether, propyleneglycol diglycidyl ether, dipropylene glycol diglycidyl ether, andcombinations thereof. Such di-epoxy compounds are available commercially(e.g., those DENACOL series di-epoxy compounds from Nagase ChemteXCorporation).

Any suitable C₁₀-C₂₄ di-azlactone compounds can be used in theinvention. Examples of such diazlactone compounds are those described inU.S. Pat. No. 4,485,236 (herein incorporated by reference in itsentirety).

Preferred examples of aziridine-containing vinylic monomers includewithout limitation 3-(1-aziridinyl) propyl(meth)acrylate,4-(1-aziridinyl) butyl(meth)acrylate, 6-(1-aziridinyl)hexyl(meth)acrylate, and 8-(1-aziridinyl) octyl(meth)acrylate).

Preferred examples of epoxy-containing vinylic monomers include withoutlimitation glycidyl(meth)acrylate, vinyl glycidyl ether, and allylglycidyl ether.

Preferred examples of azlactone-containing vinylic monomers includewithout limitation 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one,2-vinyl-4-methyl-4-ethyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one,2-vinyl-4,4-dibutyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one,2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one,2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one,2-vinyl-4,4-diethyl-1,3-oxazolin-5-one,2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-phenyl-1,3-oxazolin-5-one,2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one,2-vinyl-4,4-pentamethylene-1,3-oxazolin-5-one, and2-vinyl-4,4-dimethyl-1,3-oxazolin-6-one (with2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one (VDMO) and2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one (IPDMO) as most preferredazlactone-containing vinylic monomers).

The reactions conditions for the above described coupling reactions aretaught in textbooks and are well known to a person skilled in the art.

This aspect of the invention also is related to another class ofazetidinium-containing vinylic monomers of the invention represented byformula (2)

in which: p1, p2, and p3 independent of one another are zero or 1; R″ ishydrogen or methyl; Y₄ is a linkage selected from the group consistingof a direct bond, —O—, —NR′—, —C(O)—NR′—, —NR′—C(O)—, —O—C(O)—NH—,—NH—C(O)—O—, —NR′—C(O)—NH—, —NH—C(O)—NR′—, —C(O)—O—, —O—C(O)—, R′ ishydrogen, a C₁-C₂₀ unsubstituted or substituted, linear or branchedalkyl group; Z₄, is a direct bond, a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkylene divalent radical optionallycontaining therein one or more linkages of —O—, —NR′—, and —C(O) —, aC₁-C₇ alkyleneoxy C₁-C₇ alkylene divalent radical, or a divalent radicalof —(CH(R″)CH₂O)_(r1)—CH(R″)CH₂— in which R″ is as defined above and r1is an integer of 1 to 20; and Z₅ is a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkyl group,—(CH₂)_(r2)—O—(CH₂CH₂O)_(r1)—Z₆ in which r1 is as defined above, r2 iszero or an integer of 1 to 7, and Z₆ is a C₁-C₅ alkyl.

This class of azetidinium-containing vinylic monomers can be prepared byreacting epichlorohydrin directly with a vinylic monomer having asecondary amine group (NH) under reaction conditions known to a personskilled in the art. Examples of vinylic monomers includes withoutlimitation: N-allyl C₁-C₁₂ alkanamine (e.g., N-ethyl-2-methylallylamine,N-ethylallylamine, N-allylmethylamine, N-allyl-1-pentanamine,N-allyl-2-methyl-1-pentanamine, N-Allyl-2,3-dimethyl-1-pentanamine,N-allyl-1-hexanamine, N-allyl-2-methyl-1-hexanamine,N-allyl-1-heptanamine, N-allyl-1-octanamine, N-allyl-1-ecanamine,N-allyl-1-dodecanamine); a secondary amine-containing vinylic monomerwhich is obtained either by reacting an epoxy compound having one soleepoxy group (e.g., 1,2-epoxy C₃-C₁₂ alkanes, or mono-epoxy terminatedpolyethyleneglycol) with allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylate, or amino-C₂-C₆ alkyl(meth)acrylamide or by reactingan C₁-C₁₂ alkanamine or amino-C₂-C₁₂ alkanol or with an epoxy-containingvinylic monomer (e.g., glycidyl(meth)acrylate, vinyl glycidyl ether, orallyl glycidyl ether) under coupling reaction conditions well known to aperson skilled in the art.

An azetidinium-containing vinylic monomer of the invention can findparticular use in preparing copolymers suitable for forming non-siliconehydrogel coatings on SiHy contact lenses and/or for forming an anchoringprime coating on SiHy contact lenses.

The invention, in another aspect, provides an azetidinium-containingcopolymer comprising azetidinium-containing monomeric units derived fromat least one vinylic monomer having an azetidinium group (preferablyfrom an azetidinium-containing vinylic monomer of formula (1) or (2) asdescribed above) and monomeric units derived from at least one vinylicmonomer selected from the group consisting of a carboxyl-containingvinylic monomer, an amino-containing vinylic monomer, a hydrophobicvinylic monomer, and combination thereof.

Examples of preferred carboxyl-containing vinylic monomers includewithout limitation acrylic acid, a C₁-C₄-alkyl acrylic acid (e.g.,methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylicacid), N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonicacid), alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbicacid, angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3,itaconic acid, citraconic acid, mesaconic acid, glutaconic acid,aconitic acid, maleic acid, fumaric acid, and combination thereof.

Examples of preferred amino-containing vinylic monomers includeamino-C₂-C₄ alkyl(meth)acrylate, allylamine, vinylamine, amino-C₁-C₄alkyl(meth)acrylamide, N-allyl C₁-C₁₂ alkanamine (e.g.,N-ethyl-2-methylallylamine, N-ethylallylamine, N-allylmethylamine,N-allyl-1-pentanamine, N-allyl-2-methyl-1-pentanamine,N-allyl-2,3-dimethyl-1-pentanamine, N-allyl-1-hexanamine,N-allyl-2-methyl-1-hexanamine, N-allyl-1-heptanamine,N-allyl-1-octanamine, N-allyl-1-ecanamine, N-allyl-1-dodecanamine), acoupling reaction product of an epoxy compound having one sole epoxygroup (e.g., 1,2-epoxy C₃-C₁₂ alkanes, or mono-epoxy terminatedpolyethyleneglycol) with allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylate, or amino-C₂-C₆ alkyl(meth)acrylamide, a couplingreaction product of an C₁-C₁₂ alkanamine or C₂-C₁₂ aminoalkanol or withan epoxy-containing vinylic monomer (e.g., glycidyl(meth)acrylate, vinylglycidyl ether, or allyl glycidyl ether), and combinations thereof.

Examples of preferred hydrophobic vinylic monomers includemethyl(meth)acrylate, ethyl(meth)acrylate, propyl(meth)acrylate,isopropyl(meth)acrylate, butyl(meth)acrylate, sec-butyl(meth)acrylate,isobutyl(meth)acrylate, t-butyl(meth)acrylate, cyclohexylacrylate,2-ethylhexylacrylate, vinyl acetate, vinyl propionate, vinyl butyrate,vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidenechloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyltoluene, vinyl ethyl ether,perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornylmethacrylate, trifluoroethyl methacrylate, hexafluoro-isopropylmethacrylate, hexafluorobutyl methacrylate, siloxane-containing vinylicmonomer, a polysiloxane-containing vinylic monomer (having about 3 toabout 40 silicone atoms), and combinations thereof.

Examples of preferred siloxane-containing vinylic monomers includeN-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide,N-[tris(dimethylpropyksiloxy)silylpropyl](meth)acrylamide,N-[tris(dimethylphenylsiloxy)-silylpropyl](meth)acrylamide,N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide,N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methylacrylamide,N-(2-hydroxy-3-(3-(bis(trimethyl-silyloxy)methylsilyl)propyloxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methyl acrylamide,N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]acrylamide,N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)-propyloxy)propyl)-2-methylacrylamide,N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)-propyl)acrylamide,N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methylacrylamide,N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide,N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide,N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide,N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)-propyloxy)propyl]-2-methylacrylamide,N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)-propyl]acrylamide,3-methacryloxy propylpentamethyldisiloxane,tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS),(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane),(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane,N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)-propylvinyl carbonate,3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane,3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate,t-butyldimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl vinylcarbonate, trimethylsilylmethyl vinyl carbonate, and combinationsthereof.

A “polysiloxane-containing vinylic monomer” refers to a vinylic monomercomprising one sole ethylenically-unsaturated group and at least onepoly(di-C₁-C₆ alkyl-substituted siloxane) segment. Examples of preferredpolysiloxane-containing vinylic monomer having about 3 to about 40silicone atoms include mono-(meth)acrylate-terminatedpolydimethylsiloxanes of various molecular weight (e.g.,mono-3-methacryloxypropyl terminated, mono-C₁-C₄ alkyl terminatedpolydimethylsiloxane, or mono-(3-methacryloxy-2-hydroxypropyloxy)propylterminated, mono-C₁-C₄ alkyl terminated polydimethylsiloxane),mono-vinyl-terminated polydimethylsiloxanes,mono-(meth)acrylamide-terminated polydimethylsiloxanes,mono-vinylcarbamate-terminated polydimethylsiloxanes,mono-vinylcarbonate-terminated polydimethylsiloxanes, and combinationsthereof. Alternatively, monoethylenically functionalized polysiloxanescan be obtained by ethylenically functionalizing of a monofunctionalizedpolysiloxanes (i.e., with one sole terminal functional group, such as,e.g., —NH₂, —OH, —COOH, epoxy group, halide, etc.) as described above.Suitable monofunctionalized polysiloxanes are commercially available,e.g., from Aldrich, ABCR GmbH & Co., Fluorochem, or Gelest, Inc,Morrisville, Pa.

It is reported that the hydrogen dissociation constants (pKa) are about4.0 for polyacrylic acid, about 5.3 for polymethacrylic acid, about 6.3for polyethylacrylic acid, about 6.7 for polypropylacrylic acid, andabout 7.4 for polybutylacrylic acid (see, H. Dong, J. Phys. Chem. A 112(49): 12687-12694 (2008); F. Mitsuko, R. Grubbs, and J. D.Baldeschwieler, J. Colloid Interface Sci. 185: 210-216 (1997); S. J.Grainger and E. H. El-Sayed, in Biologically-Responsive HybridBiomaterials: A Reference for Material Scientists and Bioengineers, E.Jabbari et A. Khademhosseini, Eds., Boston, Mass.: Artech Publishing(2010), Chapter 7, pp 171-190). Because of the differences in pKa, theionization degrees of the carboxyl groups of those polymers at neutralpH can be significantly different and can have different levels ofuptake of positively-charged antimicrobial agents (e.g., PHMB, aldox,POLYQUAD, etc.) present in lens care solutions. It is believed thatwhere the azetidinium-containing polymer for a coating on a SiHy contactlens is composed primarily of methacrylic acid or ethylacrylic acid, theuptake of those positively-charged antimicrobial agents present in lenscare solutions can be minimized.

In a preferred embodiment, an azetidinium-containing copolymer of theinvention preferably comprises: azetidinium-containing monomeric unitsderived from at least one azetidinium-containing vinylic monomer offormula (1) or (2) (as described above); and carboxyl-containingmonomeric units derived from a carboxyl-containing vinylic monomer(preferably selected from the group consisting of acrylic acid,methacrylic acid, ethylacrylic acid, propylacrylic acid, maleic acid,and combinations thereof, more preferably selected from the groupconsisting of methacrylic acid, ethylacrylic acid, and combinationthereof, even more preferably derived from methacrylic acid); andoptionally amino-containing monomeric units derived from at least oneamino-containing vinylic monomer [preferably selected from the groupconsisting of amino-C₂-C₄ alkyl(meth)acrylate, allylamine, vinylamine,amino-C₁-C₄ alkyl(meth)acrylamide, N-allyl C₁-C₁₂ alkanamine (e.g.,N-ethyl-2-methylallylamine, N-ethylallylamine, N-allylmethylamine,N-allyl-1-pentanamine, N-allyl-2-methyl-1-pentanamine,N-allyl-2,3-dimethyl-1-pentanamine, N-allyl-1-hexanamine,N-allyl-2-methyl-1-hexanamine, N-allyl-1-heptanamine,N-allyl-1-octanamine, N-allyl-1-ecanamine, N-allyl-1-dodecanamine), acoupling reaction product of an epoxy compound having one sole epoxygroup (e.g., 1,2-epoxy C₃-C₁₂ alkanes, or mono-epoxy terminatedpolyethyleneglycol) with allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylate, or amino-C₂-C₆ alkyl(meth)acrylamide, a couplingreaction product of an C₁-C₁₂ alkanamine or C₂-C₁₂ aminoalkanol or withan epoxy-containing vinylic monomer (e.g., glycidyl(meth)acrylate, vinylglycidyl ether, or allyl glycidyl ether), and combinations thereof].

In another preferred embodiment, an azetidinium-containing copolymer ofthe invention preferably comprises: azetidinium-containing monomericunits derived from at least one azetidinium-containing vinylic monomerof formula (1) or (2) (as described above); carboxyl-containingmonomeric units derived from a carboxyl-containing vinylic monomerpreferably selected from the group consisting of acrylic acid,methacrylic acid, ethylacrylic acid, propylacrylic acid, maleic acid,and combinations thereof (more preferably selected from the groupconsisting of methacrylic acid, ethylacrylic acid, and combinationthereof, even more preferably derived from methacrylic acid); andhydrophobic monomeric units derived from at least one hydrophobicvinylic monomer (preferably selected from the group consisting ofmethyl(meth)acrylate, ethyl(meth)acrylate, propyl(meth)acrylate,isopropyl(meth)acrylate, butyl(meth)acrylate, sec-butyl(meth)acrylate,isobutyl(meth)acrylate, t-butyl(meth)acrylate, cyclohexylacrylate,2-ethylhexylacrylate, vinyl acetate, vinyl propionate, vinyl butyrate,vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidenechloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyltoluene, vinyl ethyl ether,perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornylmethacrylate, trifluoroethyl methacrylate, hexafluoro-isopropylmethacrylate, hexafluorobutyl methacrylate, siloxane-containing vinylicmonomer, a polysiloxane-containing vinylic monomer having about 3 toabout 40 silicone atoms, and combinations thereof, more preferablyselected from the group consisting of at least one siloxane-containingvinylic monomer, at least one polysiloxane-containing vinylic monomerand combinations thereof); and optionally amino-containing monomericunits derived from at least one amino-containing vinylic monomer[preferably selected from the group consisting of amino-C₂-C₄alkyl(meth)acrylate, allylamine, vinylamine, amino-C₁-C₄alkyl(meth)acrylamide, N-allyl C₁-C₁₂ alkanamine (e.g.,N-ethyl-2-methylallylamine, N-ethylallylamine, N-allylmethylamine,N-allyl-1-pentanamine, N-allyl-2-methyl-1-pentanamine,N-allyl-2,3-dimethyl-1-pentanamine, N-allyl-1-hexanamine,N-allyl-2-methyl-1-hexanamine, N-allyl-1-heptanamine,N-allyl-1-octanamine, N-allyl-1-ecanamine, N-allyl-1-dodecanamine), acoupling reaction product of an epoxy compound having one sole epoxygroup (e.g., 1,2-epoxy C₃-C₁₂ alkanes, or mono-epoxy terminatedpolyethyleneglycol) with allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylate, or amino-C₂-C₆ alkyl(meth)acrylamide, a couplingreaction product of an C₁-C₁₂ alkanamine or C₂-C₁₂ aminoalkanol or withan epoxy-containing vinylic monomer (e.g., glycidyl(meth)acrylate, vinylglycidyl ether, or allyl glycidyl ether), and combinations thereof].

In another preferred embodiment, an azetidinium-containing copolymer ofthe invention preferably comprises: azetidinium-containing monomericunits derived from at least one azetidinium-containing vinylic monomerof formula (1) or (2) (as described above); hydrophobic monomeric unitsderived from at least one hydrophobic vinylic monomer (preferablyselected from the group consisting of methyl(meth)acrylate,ethyl(meth)acrylate, propyl(meth)acrylate, isopropyl(meth)acrylate,butyl(meth)acrylate, sec-butyl(meth)acrylate, isobutyl(meth)acrylate,t-butyl(meth)acrylate, cyclohexylacrylate, 2-ethylhexylacrylate, vinylacetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene,chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile,1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl ethylether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate,isobornyl methacrylate, trifluoroethyl methacrylate,hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate,siloxane-containing vinylic monomer, a polysiloxane-containing vinylicmonomer having about 3 to about 40 silicone atoms, and combinationsthereof, more preferably selected from the group consisting of at leastone siloxane-containing vinylic monomer, at least onepolysiloxane-containing vinylic monomer, and combinations thereof); andoptionally amino-containing monomeric units derived from at least oneamino-containing vinylic monomer [preferably selected from the groupconsisting of amino-C₂-C₄ alkyl(meth)acrylate, allylamine, vinylamine,amino-C₁-C₄ alkyl(meth)acrylamide, N-allyl C₁-C₁₂ alkanamine (e.g.,N-ethyl-2-methylallylamine, N-ethylallylamine, N-allylmethylamine,N-allyl-1-pentanamine, N-allyl-2-methyl-1-pentanamine,N-allyl-2,3-dimethyl-1-pentanamine, N-allyl-1-hexanamine,N-allyl-2-methyl-1-hexanamine, N-allyl-1-heptanamine,N-allyl-1-octanamine, N-allyl-1-ecanamine, N-allyl-1-dodecanamine), acoupling reaction product of an epoxy compound having one sole epoxygroup (e.g., 1,2-epoxy C₃-C₁₂ alkanes, or mono-epoxy terminatedpolyethyleneglycol) with allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylate, or amino-C₂-C₆ alkyl(meth)acrylamide, a couplingreaction product of an C₁-C₁₂ alkanamine or C₂-C₁₂ aminoalkanol or withan epoxy-containing vinylic monomer (e.g., glycidyl(meth)acrylate, vinylglycidyl ether, or allyl glycidyl ether), and combinations thereof].

In another preferred embodiment, an azetidinium-containing copolymer ofthe invention preferably comprises: (1) azetidinium-containing monomericunits derived from at least one azetidinium-containing vinylic monomerof formula (1) or (2) (as described above); (2) reactive monomeric unitswhich are carboxyl-containing monomeric units and/or amino-containingmonomeric units, wherein the carboxyl-containing monomeric units arederived from at least one carboxyl-containing vinylic monomer (any oneof the those described above) and wherein the amino-containing vinylicmonomeric units are derived from at least one amino-containing vinylicmonomer (any one of those described above); and (3) at least about 50%,preferably at least about 60%, more preferably at least about 70%, evenmore preferably at least about 75% by moles of non-reactive hydrophilicmonomeric units derived from at least one hydrophilic vinylic monomerselected from the group consisting of (meth)acrylamide,N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone,N,N,-dimethylaminoethyl(meth)acrylate,N,N-dimethylaminopropyl(meth)acrylamide, glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide,N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinylalcohol (hydrolyzed form of vinyl acetate in the copolymer), aphosphorylcholine-containing vinylic monomer (including(meth)acryloyloxyethyl phosphorylcholine and those described in U.S.Pat. No. 5,461,433, herein incorporated by reference in its entirety), asugar-containing vinylic monomer (e.g., erythritol (meth)acrylate,arabitol (meth)acrylate, mannitol (meth)acrylate, ducitol(meth)acrylate, fucitol (meth)acrylate, iditol (meth)acrylate, innositol(meth)acrylate, xylitol (meth)acrylate, sorbitol (meth)acrylate, glucose(meth)acrylate, fructose (meth)acrylate, galactose (meth)acrylate, andcombinations thereof (preferably selected from the group consisting of(meth)acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone,N,N,-dimethylaminoethyl(meth)acrylate, glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, C₁-C₄-alkoxy polyethylene glycol(meth)acrylate having a weight average molecular weight of up to 1500Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl-N-methylacetamide, allyl alcohol, a phosphorylcholine-containing vinylic monomer(including (meth)acryloyloxyethyl phosphorylcholine and those describedin U.S. Pat. No. 5,461,433, herein incorporated by reference in itsentirety), erythritol (meth)acrylate, arabitol (meth)acrylate, mannitol(meth)acrylate, ducitol (meth)acrylate, fucitol (meth)acrylate, iditol(meth)acrylate, innositol (meth)acrylate, xylitol (meth)acrylate,sorbitol (meth)acrylate, glucose (meth)acrylate, fructose(meth)acrylate, galactose (meth)acrylate, and combinations thereof).More preferably, the copolymer comprises up to about 50%, preferablyfrom about 2.5% to about 40%, more preferably from about 5% to about30%, even more preferably from about 7.5% to about 25% by moles ofazetidinium-containing monomeric units and reactive monomeric units.

The weight average molecular weight M_(w) of an azetidinium-containingcopolymer of the invention is at least about 10,000 Daltons, preferablyat least about 50,000 Daltons, more preferably at least about 100,000Daltons, even more preferably from about 200,000 to about 1,000,000Daltons.

A person skilled in the art knows well how to prepare anazetidinium-containing copolymer of the invention according to any knownpolymerization technique.

An azetidinium-containing copolymer of the invention can find particularuse in forming crosslinked hydrophilic coatings on SiHy contact lenses.

The invention, in a further aspect, provides a method for producingcoated silicone hydrogel contact lenses each having a crosslinkedhydrophilic coating thereon, the method of invention comprising thesteps of: (a) obtaining a silicone hydrogel contact lens; (b) applying aprime coating of an anchoring polymer onto the silicone hydrogel contactlens, wherein the anchoring polymer is a homopolymer or copolymer of acarboxyl-containing vinylic monomer and/or an azetidinium-containingcopolymer which comprises first azetidinium-containing monomeric unitsderived from at least one azetidinium-containing vinylic monomer(preferably of formula (1) or (2) as described above) and monomericunits selected from the group consisting of carboxyl-containingmonomeric units derived from at least one carboxyl-containing vinylicmonomer (any one of those described above), amino-containing monomericunits derived from at least one amino-containing vinylic monomer (anyone of those described above), hydrophobic monomeric units derived fromat least one hydrophobic vinylic monomer (any one of those describedabove), and combinations thereof; and (c) heating the silicone hydrogelcontact lens in an aqueous solution in the presence of a water-soluble,thermally-crosslinkable hydrophilic polymeric material comprisingreactive functional groups selected from the group consisting ofazetidinium groups, carboxyl groups, amino groups, thiol groups andcombinations thereof, to and at a temperature from about 40° C. to about140° C. for a period of time sufficient to induce intermolecular andintramolecular crosslinking reaction between one azetidinium group andone amino or carboxyl group, thereby forming a durable non-siliconehydrogel coating on the silicone hydrogel contact lens, provided that atleast one of the anchoring polymer and the thermally crosslinkablehydrophilic polymeric material comprises azetidinium groups.

A person skilled in the art knows very well how to make contact lenses.For example, contact lenses can be produced in a conventional“spin-casting mold,” as described for example in U.S. Pat. No.3,408,429, or by the full cast-molding process in a static form, asdescribed in U.S. Pat. Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464;and 5,849,810, or by lathe cutting of silicone hydrogel buttons as usedin making customized contact lenses. In cast-molding, a lens formulationtypically is dispensed into molds and cured (i.e., polymerized and/orcrosslinked) in molds for making contact lenses. For production ofsilicone hydrogel (SiHy) contact lenses, a SiHy lens-forming composition(or SiHy lens formulation) for cast-molding or spin-cast molding or formaking SiHy rods used in lathe-cutting of contact lenses generallycomprises at least one components selected from the group consisting ofa silicone-containing vinylic monomer, a silicone-containing vinylicmacromer, a silicone-containing prepolymer, a hydrophilic vinylicmonomer, a hydrophobic vinylic monomer, a crosslinking agent (a compoundhaving a molecular weight of about 700 Daltons or less and containing atleast two ethylenically unsaturated groups), a free-radical initiator(photoinitiator or thermal initiator), a hydrophilic vinylicmacromer/prepolymer, and combination thereof, as well known to a personskilled in the art. A SiHy contact lens formulation can also compriseother necessary components known to a person skilled in the art, suchas, for example, a UV-absorbing agent, a visibility tinting agent (e.g.,dyes, pigments, or mixtures thereof), antimicrobial agents (e.g.,preferably silver nanoparticles), a bioactive agent, leachablelubricants, leachable tear-stabilizing agents, and mixtures thereof, asknown to a person skilled in the art. Resultant SiHy contact lenses thencan be subjected to extraction with an extraction solvent to removeunpolymerized components from the resultant lenses and to hydrationprocess, as known by a person skilled in the art. In addition, apreformed SiHy contact lens can be a colored contact lens (i.e., a SiHycontact lens having at least one colored patterns printed thereon aswell known to a person skilled in the art).

Numerous SiHy lens formulations including various combinations ofcomponents described above have been described in numerous patents andpatent applications published by the filing date of this application.All of them can be used in obtaining a SiHy lens to be coated. A SiHylens formulation for making commercial SiHy lenses, such as, lotrafilconA, lotrafilcon B, delefilcon A, balafilcon A, galyfilcon A, senofilconA, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, orthe like, can also be used in making SiHy contact lenses to be coated inthis invention.

In accordance with the invention, a prime coating is formed bycontacting a SiHy contact lens (to be coated) with a solution of ananchoring polymer. Contacting of the contact lens with a solution of ananchoring polymer can occur by dipping it into the coating solution orby spraying it with the coating solution. One contacting processinvolves solely dipping the contact lens in a bath of a solution of theanchoring polymer for a period of time or alternatively dipping thecontact lens sequentially in a series of bath of solutions of theanchoring polymer for a fixed shorter time period for each bath. Anothercontacting process involves solely spray a solution of the anchoringpolymer. However, a number of alternatives involve various combinationsof spraying- and dipping-steps may be designed by a person havingordinary skill in the art.

The contacting time of a contact lens with a solution of the anchoringpolymer may last up to about 10 minutes, preferably from about 5 toabout 360 seconds, more preferably from about 5 to about 250 seconds,even more preferably from about 5 to 200 seconds.

In accordance with the invention, the anchoring polymer is a linear orbranched or crosslinked polymer, so long as it is soluble in water, anorganic solvent, a mixture of two or more organic solvents, a mixture ofwater with one or more organic solvent.

All the embodiments and preferred embodiments of carboxyl-containingvinylic monomers, azetidinium-containing vinylic monomers,amino-containing vinylic monomers, hydrophobic vinylic monomers,non-reactive hydrophilic vinylic monomers, and azetidinium-containingcopolymers have been described above and can be used in this aspect ofthe invention.

In a preferred embodiment, an anchoring polymer of the inventionpreferably comprises carboxyl-containing monomeric units derived from acarboxyl-containing vinylic monomer preferably selected from the groupconsisting of acrylic acid, methacrylic acid, ethylacrylic acid,propylacrylic acid, maleic acid, and combinations thereof, morepreferably selected from the group consisting of methacrylic acid,ethylacrylic acid, and combination thereof, even more preferably derivedfrom methacrylic acid.

In another preferred embodiment, the anchoring polymer is: polyacrylicacid (PAA); polymethacrylic acid (PMAA); polyethylacrylic acid,polypropylacrylic acid; a copolymer of at least two vinylic monomersselected from the group consisting of acrylic acid, methacrylic acid,ethylacrylic acid, and propylacrylic acid; polymaleic acid (i.e.,partially or fully hydrolyzed polymaleic anhydride); a copolymer ofmaleic acid and one or more vinylic monomers (e.g., ethylene, methylvinyl ether, vinyl acetate, and/or isobutylene); a copolymer composed offrom about 0.05% to about 20% (preferably from about 0.1% to about 15%,more preferably from about 0.5% to about 10%) by moles of anazetidinium-containing vinylic monomer (preferably anazetidinium-containing vinylic monomer of formula (1) as describedabove) and of from about 80% to about 99.95% by moles of one or morecarboxyl-containing vinylic monomers selected from the group consistingof acrylic acid, methacrylic acid, ethylacrylic acid, propylacrylicacid, and combination thereof; a reaction product of an azetidiniumcompound of

in which T₇ and T₈ as defined above with polymaleic anhydride or with acopolymer of maleic anhydride and one or more vinylic monomers (e.g.,ethylene, methyl vinyl ether, vinyl acetate, and/or isobutylene),wherein the molar equivalent ratio of the azetidinium compound to maleicanhydride is about 0.25 or less (preferably about 0.2 or less, morepreferably about 0.15 or less, even more preferably about 0.1 or less);and combinations thereof.

In another preferred embodiment, an anchoring polymer of the inventionpreferably comprises: carboxyl-containing monomeric units derived from acarboxyl-containing vinylic monomer preferably selected from the groupconsisting of acrylic acid, methacrylic acid, ethylacrylic acid,propylacrylic acid, maleic acid, and combinations thereof (morepreferably selected from the group consisting of methacrylic acid,ethylacrylic acid, and combination thereof, even more preferably derivedfrom methacrylic acid); and azetidinium-containing monomeric unitsderived from at least one azetidinium-containing vinylic monomer offormula (1) or (2) (as described above).

In another preferred embodiment, an anchoring polymer of the inventionpreferably comprises: carboxyl-containing monomeric units derived from acarboxyl-containing vinylic monomer preferably selected from the groupconsisting of acrylic acid, methacrylic acid, ethylacrylic acid,propylacrylic acid, maleic acid, and combinations thereof (morepreferably selected from the group consisting of methacrylic acid,ethylacrylic acid, and combination thereof, even more preferably derivedfrom methacrylic acid); azetidinium-containing monomeric units derivedfrom at least one azetidinium-containing vinylic monomer of formula (1)or (2) (as described above); and hydrophobic monomeric units derivedfrom at least one hydrophobic vinylic monomer (preferably from at leastone siloxane-containing vinylic monomer and/or at least onepolysiloxane-containing vinylic monomer).

In another preferred embodiment, an anchoring polymer of the inventionpreferably comprises: azetidinium-containing monomeric units derivedfrom at least one azetidinium-containing vinylic monomer of formula (1)or (2) (as described above); and hydrophobic monomeric units derivedfrom at least one hydrophobic vinylic monomer (preferably from at leastone siloxane-containing vinylic monomer and/or at least onepolysiloxane-containing vinylic monomer).

In another preferred embodiment, an anchoring polymer of the inventionpreferably comprises: carboxyl-containing monomeric units derived from acarboxyl-containing vinylic monomer preferably selected from the groupconsisting of acrylic acid, methacrylic acid, ethylacrylic acid,propylacrylic acid, maleic acid, and combinations thereof (morepreferably selected from the group consisting of methacrylic acid,ethylacrylic acid, and combination thereof, even more preferably derivedfrom methacrylic acid); and hydrophobic monomeric units derived from atleast one hydrophobic vinylic monomer (preferably from at least onesiloxane-containing vinylic monomer and/or at least onepolysiloxane-containing vinylic monomer).

The weight average molecular weight M_(w) of an anchoring polymer forforming an anchoring prime coating is at least about 10,000 Daltons,preferably at least about 50,000 Daltons, more preferably at least about100,000 Daltons, even more preferably from about 200,000 to about1,000,000 Daltons.

A solution of an anchoring polymer for forming a prime coating oncontact lenses can be prepared by dissolving one or more anchoringpolymers in water, a mixture of water and an organic solvent misciblewith water, an organic solvent, or a mixture of one or more organicsolvent. Preferably, the anchoring polymer is dissolved in a mixture ofwater and one or more organic solvents, an organic solvent, or a mixtureof one or more organic solvent. It is believed that a solvent systemcontaining at least one organic solvent can swell a silicone hydrogelcontact lens so that a portion of the anchoring polymer may penetrateinto the silicone hydrogel contact lens and increase the durability ofthe prime coating.

Any organic solvents can be used in preparation of a solution of ananchoring polymer. Examples of organic solvents include withoutlimitation tetrahydrofuran, tripropylene glycol methyl ether,dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones(e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butylether, diethylene glycol methyl ether, ethylene glycol phenyl ether,propylene glycol methyl ether, propylene glycol methyl ether acetate,dipropylene glycol methyl ether acetate, propylene glycol n-propylether, dipropylene glycol n-propyl ether, tripropylene glycol n-butylether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether,tripropylene glycol n-butyl ether, propylene glycol phenyl etherdipropylene glycol dimethyl ether, polyethylene glycols, polypropyleneglycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate,ethyl lactate, i-propyl lactate, methylene chloride, methanol, ethanol,1- or 2-propanol, 1- or 2-butanol, tert-butanol, tert-amyl alcohol,menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol,3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol,2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol,2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol,1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol,1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol,2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol,3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol,4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol,3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol,4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol,2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol,1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene,4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol,2-methoxy-2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol,3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanoland 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-pyrrolidone,N,N-dimethylpropionamide, dimethyl formamide, dimethyl acetamide,dimethyl propionamide, N-methylpyrrolidinone, and mixtures thereof.

In accordance with this aspect of the invention, wherein thewater-soluble, thermally-crosslinkable hydrophilic polymeric materialcan be any water-soluble polymer so long as it contains reactive groupsselected from the group consisting of azetidinium groups, carboxylgroups, amino groups, thiol groups, and combinations thereof.Preferably, a water-soluble, thermally crosslinkable hydrophilicpolymeric material is: (i) an azetidinium-containing copolymer of theinvention (as those described above and can be used here) comprisingcomprises at least about 50%, preferably at least about 60%, morepreferably at least about 70%, even more preferably at least about 75%by moles of non-reactive hydrophilic monomeric units derived from atleast one hydrophilic vinylic monomer (any one of those describedabove); (ii) a reaction product of an azetidinium-containing copolymer(as those described above and can be used here) being free of anysilicone with at least one hydrophilicity-enhancing agent having atleast one reactive functional group selected from the group consistingof amino group, carboxyl group, thiol group, and combinations thereof;(iii) a reaction product of polyaminoamide-epichlorohydrin with at leastone hydrophilicity-enhancing agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combinations thereof; and (iv) awater-soluble hydrophilic polymer having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combinations thereof.

The term “hydrophilicity-enhancing agent” refers to a hydrophilicorganic compound or polymer that can reacted with anazetidinium-containing copolymer of the invention to form a product withthe hydrophilicity-enhancing agent covalently incorporated therein ashydrophilic moieties and/or hydrophilic chains. Any suitablehydrophilicity-enhancing agents can be used in the invention so long asthey contain at least one amino group, at least one carboxyl group,and/or at least one thiol group.

A preferred class of hydrophilicity-enhancing agents include withoutlimitation: amino-, carboxyl- or thiol-containing monosaccharides (e.g.,3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid,galactosamine, glucosamine, galacturonic acid, gluconic acid,glucosaminic acid, mannosamine, saccharic acid 1,4-lactone, saccharideacid, Ketodeoxynonulosonic acid, N-methyl-D-glucamine,1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol,1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); amino-,carboxyl- or thiol-containing disaccharides (e.g., chondroitindisaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonicacid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionicacid); and amino-, carboxyl- or thiol-containing oligosaccharides (e.g.,carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); andcombinations thereof.

Another preferred class of hydrophilicity-enhancing agents ishydrophilic polymers having one or more amino, carboxyl and/or thiolgroups. More preferably, the content of monomeric units having an amino(—NHR′ with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH)group in a hydrophilic polymer as a hydrophilicity-enhancing agent isless than about 40%, preferably less than about 30%, more preferablyless than about 20%, even more preferably less than about 10%, by weightbased on the total weight of the hydrophilic polymer.

One preferred class of hydrophilic polymers as hydrophilicity-enhancingagents are amino- or carboxyl-containing polysaccharides, for example,such as, carboxymethylcellulose (having a carboxyl content of about 40%or less, which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(CH₂CO₂H)_(m)]— in which m is 1 to 3),carboxyethylcellulose (having a carboxyl content of about 36% or less,which is estimated based on the composition of repeating units,[C₆H_(10-m)O₅(C₂H₄CO₂H)_(m)]— in which m is 1 to 3)carboxypropylcellulose (having a carboxyl content of about 32% or less,which is estimated based on the composition of repeating units,[C₆H_(10-m)O₅(C₃H₆CO₂H)_(m)]—, in which m is 1 to 3), hyaluronic acid(having a carboxyl content of about 11%, which is estimated based on thecomposition of repeating units, —(C₁₃H₂₀O₉NCO₂H)—), chondroitin sulfate(having a carboxyl content of about 9.8%, which is estimated based onthe composition of repeating units, —(C₁₂H₁₈O₁₃NS CO₂H)—), orcombinations thereof.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents include without limitation:poly(ethylene glycol) (PEG) with mono-amino, carboxyl or thiol group(e.g., PEG-NH₂, PEG-SH, PEG-COOH); H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl or thiol groups; PEG dendrimers with one or moreamino, carboxyl or thiol groups; a diamino- or dicarboxyl-terminatedhomo- or co-polymer of a non-reactive hydrophilic vinylic monomer; amonoamino- or monocarboxyl-terminated homo- or co-polymer of anon-reactive hydrophilic vinylic monomer; a copolymer which is apolymerization product of a composition comprising (1) about 60% byweight or less, preferably from about 0.1% to about 30%, more preferablyfrom about 0.5% to about 20%, even more preferably from about 1% toabout 15%, by weight of one or more reactive vinylic monomers and (2) atleast one non-reactive hydrophilic vinylic monomer and/or at least onephosphorylcholine-containing vinylic monomer; and combinations thereof.Reactive vinylic monomer(s) and non-reactive hydrophilic vinylicmonomer(s) are those described previously.

More preferably, a hydrophilic polymer as a hydrophilicity-enhancingagent is PEG-NH₂; PEG-SH; PEG-COOH; H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl or thiol groups; PEG dendrimers with one or moreamino, carboxyl or thiol groups; a monoamino-, monocarboxyl-, diamino-or dicarboxyl-terminated homo- or copolymer of a non-reactivehydrophilic vinylic monomer selected from the group consisting ofacrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone(NVP), N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol,N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone,N,N-dimethylaminoethyl(meth)acrylate,N,N-dimethylaminopropyl(metha)crylamide, (meth)acryloyloxyethylphosphorylcholine, and combinations thereof; a copolymer which is apolymerization product of a composition comprising (1) from about 0.1%to about 30%, preferably from about 0.5% to about 20%, more preferablyfrom about 1% to about 15%, by weight of (meth)acrylic acid, C₂-C₁₂alkylacrylic acid, vinylamine, allylamine, and/or amino-C₂-C₄alkyl(meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholineand/or at least one non-reactive hydrophilic vinylic monomer selectedfrom the group consisting of acrylamide, N,N-dimethylacrylamide,N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol, and combination thereof.

Most preferably, the hydrophilicity-enhancing agent as ahydrophilicity-enhancing agent is PEG-NH₂; PEG-SH; PEG-COOH; monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated polyvinylpyrrolidone;monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpolyacrylamide; monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(DMA); monoamino- or monocarboxyl-, diamino-or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminatedpoly(NVP-co-N,N-dimethylaminoethyl(meth)acrylate)); monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated poly(vinylalcohol);monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly[(meth)acryloyloxyethyl phosphrylcholine] homopolymer or copolymer;monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly(NVP-co-vinyl alcohol); monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylicacid-co-acrylamide] with from about 0.1% to about 30%, preferably fromabout 0.5% to about 20%, more preferably from about 1% to about 15%, byweight of (meth)acrylic acid; poly[(meth)acrylic acid-co-NVP) with fromabout 0.1% to about 30%, preferably from about 0.5% to about 20%, morepreferably from about 1% to about 15%, by weight of (meth)acrylic acid;a copolymer which is a polymerization product of a compositioncomprising (1) (meth)acryloyloxyethyl phosphorylcholine and (2) fromabout 0.1% to about 30%, preferably from about 0.5% to about 20%, morepreferably from about 1% to about 15%, by weight of a carboxylic acidcontaining vinylic monomer and/or an amino-containing vinylic monomer,and combination thereof.

PEGs with functional groups and multi-arm PEGs with functional groupscan be obtained from various commercial suppliers, e.g., Polyscience,and Shearwater Polymers, inc., etc.

Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymers of one or more non-reactive hydrophilic vinylic monomers orof a phosphorylcholine-containing vinylic monomer can be preparedaccording to procedures described in U.S. Pat. No. 6,218,508, hereinincorporated by reference in its entirety. For example, to prepare adiamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactivehydrophilic vinylic monomer, the non-reactive vinylic monomer, a chaintransfer agent with an amino or carboxyl group (e.g.,2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid,thiolactic acid, or other hydroxymercaptanes, aminomercaptans, orcarboxyl-containing mercaptanes) and optionally other vinylic monomerare copolymerized (thermally or actinically) with a reactive vinylicmonomer (having an amino or carboxyl group), in the presence of anfree-radical initiator. Generally, the molar ratio of chain transferagent to that of all of vinylic monomers other than the reactive vinylicmonomer is from about 1:5 to about 1:100, whereas the molar ratio ofchain transfer agent to the reactive vinylic monomer is 1:1. In suchpreparation, the chain transfer agent with amino or carboxyl group isused to control the molecular weight of the resultant hydrophilicpolymer and forms a terminal end of the resultant hydrophilic polymer soas to provide the resultant hydrophilic polymer with one terminal aminoor carboxyl group, while the reactive vinylic monomer provides the otherterminal carboxyl or amino group to the resultant hydrophilic polymer.Similarly, to prepare a monoamino- or monocarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer, thenon-reactive vinylic monomer, a chain transfer agent with an amino orcarboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid,thioglycolic acid, thiolactic acid, or other hydroxymercaptanes,aminomercaptans, or carboxyl-containing mercaptanes) and optionallyother vinylic monomers are copolymerized (thermally or actinically) inthe absence of any reactive vinylic monomer.

As used in this application, a copolymer of a non-reactive hydrophilicvinylic monomer refers to a polymerization product of a non-reactivehydrophilic vinylic monomer with one or more additional vinylicmonomers. Copolymers comprising a non-reactive hydrophilic vinylicmonomer and a reactive vinylic monomer (e.g., a carboxyl-containingvinylic monomer) can be prepared according to any well-known radicalpolymerization methods or obtained from commercial suppliers. Copolymerscontaining methacryloyloxyethyl phosphorylcholine andcarboxyl-containing vinylic monomer can be obtained from NOP Corporation(e.g., LIPIDURE® -A and -AF).

The weight average molecular weight M_(w) of the hydrophilic polymerhaving at least one amino, carboxyl or thiol group (as ahydrophilicity-enhancing agent) is preferably from about 500 to about1,000,000, more preferably from about 1,000 to about 500,000.

Polyaminoamide-epichlorohydrin (PAE) (orpolyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin) arecommercially available, such as, for example, Kymene® or Polycup® resins(epichlorohydrin-functionalized adipic acid-diethylenetriaminecopolymers) from Hercules or Polycup® or Servamine® resins fromServo/Delden. Alternatively, PAE can be obtained by reactingepichlorohydrin with a poly(amidoamine) which is a polycondensatederived from a polyamine and a dicarboxylic acid (e.g., adipicacid-diethylenetriamine copolymers). The reaction conditions forepichlorohydrin-functionalization of a polyamidoamine polymer are taughtin EP1465931 (herein incorporated by reference in its entirety).

In accordance with the invention, the reaction between ahydrophilicity-enhancing agent and an azetidinium-containing copolymerof the invention (or polyamidoamine-epichlorohydrin) is carried out at atemperature of from about 40° C. to about 100° C. for a period of timesufficient (from about 0.3 hour to about 24 hours, preferably from about1 hour to about 12 hours, even more preferably from about 2 hours toabout 8 hours) to form a water-soluble and thermally-crosslinkablehydrophilic polymeric material containing reactive functional groups(azetidinium, carboxyl, amino, and/or thiol groups).

In a preferred embodiment, the thermally-crosslinkable hydrophilicpolymeric material is an azetidinium-copolymer of the invention whichcomprises: (1) up to about 50% (preferably from about 2.5% to about 40%,more preferably from about 5% to about 30%, even more preferably fromabout 7.5% to about 25%) by moles of azetidinium-containing monomericunits (derived from at least one azetidinium-containing vinylic monomerof formula (1) or (2) as defined above) and reactive monomeric units;and (2) at least about 50%, preferably at least about 60%, morepreferably at least about 70%, even more preferably at least about 75%by moles of non-reactive hydrophilic monomeric units derived from atleast one hydrophilic vinylic monomer selected from the group consistingof (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N-vinylpyrrolidone,N,N,-dimethylaminoethyl(meth)acrylate,N,N-dimethylaminopropyl(meth)acrylamide, glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide,N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinylalcohol (hydrolyzed form of vinyl acetate in the copolymer), aphosphorylcholine-containing vinylic monomer (including(meth)acryloyloxyethyl phosphorylcholine and those described in U.S.Pat. No. 5,461,433, herein incorporated by reference in its entirety), asugar-containing vinylic monomer (e.g., erythritol (meth)acrylate,arabitol (meth)acrylate, mannitol (meth)acrylate, ducitol(meth)acrylate, fucitol (meth)acrylate, iditol (meth)acrylate, innositol(meth)acrylate, xylitol (meth)acrylate, sorbitol (meth)acrylate, glucose(meth)acrylate, fructose (meth)acrylate, galactose (meth)acrylate), andcombinations thereof.

In accordance with this aspect of the invention, the step of heating isperformed preferably by autoclaving the silicone hydrogel contact lensimmersed in a packaging solution (i.e., a buffered aqueous solution) ina sealed lens package at a temperature of from about 118° C. to about125° C. for approximately 20-90 minutes. In accordance with thisembodiment of the invention, the packaging solution is a bufferedaqueous solution which is ophthalmically safe after autoclave.

Lens packages (or containers) are well known to a person skilled in theart for autoclaving and storing a soft contact lens. Any lens packagescan be used in the invention. Preferably, a lens package is a blisterpackage which comprises a base and a cover, wherein the cover isdetachably sealed to the base, wherein the base includes a cavity forreceiving a sterile packaging solution and the contact lens.

Lenses are packaged in individual packages, sealed, and sterilized(e.g., by autoclave at about 120° C. or higher for at least 30 minutesunder pressure) prior to dispensing to users. A person skilled in theart will understand well how to seal and sterilize lens packages.

In accordance with the invention, a packaging solution contains at leastone buffering agent and one or more other ingredients known to a personskilled in the art. Examples of other ingredients include withoutlimitation, tonicity agents, surfactants, antibacterial agents,preservatives, and lubricants (e.g., cellulose derivatives, polyvinylalcohol, polyvinyl pyrrolidone).

The packaging solution contains a buffering agent in an amountsufficient to maintain a pH of the packaging solution in the desiredrange, for example, preferably in a physiologically acceptable range ofabout 6 to about 8.5. Any known, physiologically compatible bufferingagents can be used. Suitable buffering agents as a constituent of thecontact lens care composition according to the invention are known tothe person skilled in the art. Examples are boric acid, borates, e.g.sodium borate, citric acid, citrates, e.g. potassium citrate,bicarbonates, e.g. sodium bicarbonate, TRIS(2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris(Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane),bis-aminopolyols, triethanolamine, ACES(N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES(N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES(2-(N-morpholino)ethanesulfonic acid), MOPS(3-[N-morpholino]-propanesulfonic acid), PIPES(piperazine-N,N′-bis(2-ethanesulfonic acid), TES(N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), saltsthereof, phosphate buffers, e.g. Na₂HPO₄, NaH₂PO₄, and KH₂PO₄ ormixtures thereof. A preferred bis-aminopolyol is1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). Theamount of each buffer agent in a packaging solution is preferably from0.001% to 2%, preferably from 0.01% to 1%; most preferably from about0.05% to about 0.30% by weight.

The packaging solution has a tonicity of from about 200 to about 450milliosmol (mOsm), preferably from about 250 to about 350 mOsm. Thetonicity of a packaging solution can be adjusted by adding organic orinorganic substances which affect the tonicity. Suitable occularlyacceptable tonicity agents include, but are not limited to sodiumchloride, potassium chloride, glycerol, propylene glycol, polyols,mannitols, sorbitol, xylitol and mixtures thereof.

A packaging solution of the invention has a viscosity of from about 1centipoise to about 8 centipoises, more preferably from about 1.5centipoises to about 5 centipoises, at 25° C.

In a preferred embodiment, the packaging solution comprises preferablyfrom about 0.01% to about 2%, more preferably from about 0.05% to about1.5%, even more preferably from about 0.1% to about 1%, most preferablyfrom about 0.2% to about 0.5%, by weight of a thermally-crosslinkablehydrophilic polymeric material of the invention.

In another preferred embodiment, a method of the invention can furthercomprise, before the step of heating, the steps of: contacting at roomtemperature the silicone hydrogel contact lens with an aqueous solutionof the thermally-crosslinkable hydrophilic polymeric material to form atop layer (i.e., an LbL coating) of the thermally-crosslinkablehydrophilic polymeric material on the surface of the silicone hydrogelcontact lens, immersing the silicone hydrogel contact lens with the toplayer of the thermally-crosslinkable hydrophilic polymeric material in apackaging solution in a lens package; sealing the lens package; andautoclaving the lens package with the silicone hydrogel contact lenstherein to form a crosslinked hydrophilic coating on the siliconehydrogel contact lens. Because of being positively charged, thethermally-crosslinkable hydrophilic polymeric material is believed to becapable of forming, on the prime coating of a silicone hydrogel contactlens, a non-covalently-bound layer through physical interactions.

A silicone hydrogel contact lens obtained according a method of theinvention has a surface hydrophilicity/wettability characterized byhaving an averaged water contact angle of preferably about 90 degrees orless, more preferably about 80 degrees or less, even more preferablyabout 70 degrees or less, most preferably about 60 degrees or less.

All of the various embodiments including preferred embodiments of anazetidinium-containing vinylic monomer are described above and can beused in this aspect of the invention.

It should be understood that although various embodiments includingpreferred embodiments of the invention may be separately describedabove, they can be combined and/or used together in any desirablefashion in this aspect of the invention.

The invention, in another further aspect, provides a method forproducing silicone hydrogel contact lenses each having a crosslinkedhydrophilic coating thereon, the method of invention comprising thesteps of: (a) obtaining a silicone hydrogel contact lens from alens-forming composition comprising an azetidinium-containing copolymer(as described above) and/or an azetidinium-containing vinylic monomer offormula (1) or (2) as defined above; (b) heating the silicone hydrogelcontact lens in an aqueous solution in the presence of a water-soluble,thermally-crosslinkable hydrophilic polymeric material comprisingreactive groups selected from the group consisting of azetidiniumgroups, carboxyl groups, amino groups, thiol groups and combinationsthereof, to and at a temperature from about 40° C. to about 140° C. fora period of time sufficient to induce intermolecular and intramolecularcrosslinking reactions between one azetidinium group and one amino orcarboxyl group, thereby forming a durable non-silicone hydrogel coatingon the silicone hydrogel contact lens, wherein the non-silicone hydrogelcoating is anchored onto the silicone hydrogel contact lens through theazetidinium groups of the azetidinium-containing copolymer on and/ornear the surface of the silicone hydrogel contact lens.

It is believed that a portion of the azetidinium-containing copolymerand/or azetidinium-containing monomeric units may be located on and/ornear the surface of the silicone hydrogel contact lens obtained from thelens-forming composition comprising the azetidinium-containingcopolymer. Those azetidinium groups on and/or near the lens surface canserve as anchoring sites for attaching the non-silicone hydrogelcoating.

In a preferred embodiment, the azetidinium-containing copolymer iscompatible with polymerizable components in the lens-forming compositionand comprises azetidinium-containing monomeric units derived from anazetidinium-containing vinylic monomer of formula (1) or (2) as definedabove and hydrophobic monomeric units derived from a hydrophobic vinylicmonomer. More preferably, the azetidinium-containing copolymer issubstantially free (preferably free of) of any ethylenically unsaturatedgroup.

The term “compatible with polymerizable components in the lens-formingcomposition” in reference to an azetidinium-containing copolymer meansthat the lens-forming composition comprising the azetidinium-containingcopolymer and the polymerizable components has an opticaltransmissibility (between 400 nm to 700 nm) of at least about 85%, morepreferably at least about 90%, even more preferably at least about 95%,most preferably at least about 98%.

In a preferred embodiment, the method further comprises a step ofapplying a prime coating of an anchoring polymer onto the siliconehydrogel contact lens. All the embodiments (including preferredembodiments) of anchoring polymers described above can be used in thispreferred embodiment of the method of the invention in this aspect.

Preferably, the step of heating is performed by autoclaving the siliconehydrogel contact lens immersed in a packaging solution (i.e., a bufferedaqueous solution) in a sealed lens package at a temperature of fromabout 118° C. to about 125° C. for approximately 20-90 minutes.

Preferably, the packaging solution comprises from about 0.01% to about2%, preferably from about 0.05% to about 1.5%, more preferably fromabout 0.1% to about 1%, even more preferably from about 0.2% to about0.5%, by weight of the thermally-crosslinkable hydrophilic polymericmaterial.

All of the various embodiments including preferred embodiments of asilicone hydrogel contact lens, a SiHy lens formulation, anazetidinium-containing vinylic monomer, an anchoring polymer and itsuses for forming a prime coating, a water-soluble,thermally-crosslinkable hydrophilic polymeric material, the step ofheating the silicone hydrogel contact lens in an aqueous solution in thepresence of a water-soluble, thermally-crosslinkable hydrophilicpolymeric material, a lens packaging solution and components thereof,lens packages, are described above and can be combined and/or usedtogether in this aspect of the invention.

In still a further aspect, the invention provides a silicone hydrogelcontact lens comprising a lens body made of a silicone hydrogel materialand a non-silicone hydrogel coating thereon, wherein the non-siliconehydrogel coating is obtained by thermally inducing intermolecular andintramolecular crosslinking of a thermally-crosslinkable hydrophilicpolymeric material which comprises azetidinium-containing monomericunits derived from at least one azetidinium-containing vinylic monomer(preferably a monomer of formula (1) or (2) described above) andreactive monomeric units derived from a vinylic monomer having an aminoor carboxyl group, wherein the silicone hydrogel contact lens has anoxygen permeability of at least about 40 barrers, a surface wettabilitycharacterized by a water contact angle of about 100 degrees or less, anda good coating durability characterized by surviving a digital rubbingtest.

In accordance with the invention, a lens body refers of a preformedsilicone hydrogel contact lens to be coated and is obtained from asilicone hydrogel lens formulation (composition) as described above.

In a preferred embodiment, the silicone hydrogel contact lens has atleast one property selected from the group consisting of: an oxygenpermeability of at least about 50 barrers, preferably at least about 60barrers, more preferably at least about 70 barrers; an elastic modulusof about 1.5 MPa or less, preferably about 1.2 MPa or less, morepreferably about 1.0 or less, even more preferably from about 0.3 MPa toabout 1.0 MPa; a water content of preferably from about 18% to about70%, more preferably from about 20% to about 60% by weight when fullyhydrated; and combination thereof.

Various embodiments including preferred embodiments of a siliconehydrogel contact lens to be coated, azetidinium-containing vinylicmonomer, and a thermally-crosslinkable hydrophilic polymeric materialare described above and can be combined and/or used together in thisaspect of the invention.

The water content of a silicone hydrogel contact lens can be measuredaccording to Bulk Technique as disclosed in U.S. Pat. No. 5,849,811.

In still another further aspect, the invention provides an ophthalmicproduct, which comprises a sterilized and sealed lens package, whereinthe lens package comprises: a post-autoclave lens packaging solution anda readily-usable silicone hydrogel contact lens immersed therein,wherein the readily-usable silicone hydrogel contact lens comprises acrosslinked hydrophilic coating obtained by autoclaving an originalsilicone hydrogel contact lens having amino groups and/or carboxylgroups on and/or near the surface of the original silicone hydrogelcontact lens in a pre-autoclave packaging solution containing awater-soluble and thermally-crosslinkable hydrophilic polymeric materialwhich comprises from 0.001% to about 25% by mole ofazetidinium-containing monomeric units derived from at least oneazetidinium-containing vinylic monomer, wherein the hydrophilicpolymeric material is covalently attached onto the silicone hydrogelcontact lens through second covalent linkages each formed between oneamino or carboxyl group on and/or near the surface of the siliconehydrogel contact lens and one azetidinium group of the hydrophilicpolymeric material, wherein the post-autoclave packaging solutioncomprises at least one buffering agent in an amount sufficient tomaintain a pH of from about 6.0 to about 8.5 and an hydrolyzed productof the hydrophilic polymeric material and has a tonicity of from about200 to about 450 milliosmol (mOsm) and a viscosity of from about 1centipoise to about 10 centipoises.

All of the various embodiments including preferred embodiments of asilicone hydrogel contact lens, a SiHy lens formulation, anazetidinium-containing vinylic monomer, an anchoring polymer and itsuses for forming a prime coating, a water-soluble,thermally-crosslinkable hydrophilic polymeric material, the step ofheating the silicone hydrogel contact lens in an aqueous solution in thepresence of a water-soluble, thermally-crosslinkable hydrophilicpolymeric material, a lens packaging solution and components thereof,lens packages, are described above and can be combined and/or usedtogether in this aspect of the invention.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. Various modifications, variations, andcombinations can be made to the various embodiment described herein. Inorder to better enable the reader to understand specific embodiments andthe advantages thereof, reference to the following examples issuggested. It is intended that the specification and examples beconsidered as exemplary.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart or can be combined in any manner and/or used together. Therefore,the spirit and scope of the appended claims should not be limited to thedescription of the preferred versions contained therein.

EXAMPLE 1

Oxygen Permeability Measurements

The apparent oxygen permeability (Dk_(app)), the apparent oxygentransmissibility (Dk/t), the intrinsic (or edge-corrected) oxygenpermeability (Dk_(c)) of a lens and a lens material are determinedaccording to procedures described in Example 1 of U.S. patentapplication publication No. 2012/0026457 A1 (herein incorporated byreference in its entirety).

Lubricity Evaluation

The lubricity rating is a qualitative ranking scheme where 0 is assignedto control lenses coated with polyacrylic acid (PAA), 1 is assigned toOasys™/TruEye™ commercial lenses and 5 is assigned to commercial AirOptix™ lenses. The samples are rinsed with excess DI water for at leastthree times and then transferred to PBS before the evaluation. Beforethe evaluation, hands are rinsed with a soap solution, extensivelyrinsed with DI water and then dried with KimWipe® towels. The samplesare handled between the fingers and a numerical number is assigned foreach sample relative to the above standard lenses described above. Forexample, if lenses are determined to be only slightly better than AirOptix™ lenses, then they are assigned a number 4. For consistency, allratings are independently collected by the same two operators in orderto avoid bias and the data so far reveal very good qualitative agreementand consistency in the evaluation.

Surface hydrophilicity/wetability Tests. Water contact angle on acontact lens is a general measure of the surface hydrophilicity (orwetability) of the contact lens. In particular, a low water contactangle corresponds to more hydrophilic surface. Average contact angles(Sessile Drop) of contact lenses are measured using a VCA 2500 XEcontact angle measurement device from AST, Inc., located in Boston,Mass. This equipment is capable of measuring advancing or recedingcontact angles or sessile (static) contact angles. The measurements areperformed on fully hydrated contact lenses and immediately afterblot-drying as follows. A contact lens is removed from the vial andwashed 3 times in ˜200 ml of fresh DI water in order to remove looselybound packaging additives from the lens surface. The lens is then placedon top of a lint-free clean cloth (Alpha Wipe TX1009), dabbed well toremove surface water, mounted on the contact angle measurement pedestal,blown dry with a blast of dry air and finally the sessile drop contactangle is automatically measured using the software provided by themanufacturer. The DI water used for measuring the contact angle has aresistivity>18MΩcm and the droplet volume used is 2 μl. Typically,uncoated silicone hydrogel lenses (after autoclave) have a sessile dropcontact angle around 120 degrees. The tweezers and the pedestal arewashed well with Isopropanol and rinsed with DI water before coming incontact with the contact lenses.

Water Break-up Time (WBUT) Tests. The wettabilty of the lenses (afterautoclave) is also assessed by determining the time required for thewater film to start breaking on the lens surface. Briefly, lenses areremoved from the vial and washed 3 times in ˜200 ml of fresh DI water inorder to remove loosely bound packaging additives from the lens surface.The lens is removed from the solution and held against a bright lightsource. The time that is needed for the water film to break (de-wet)exposing the underlying lens material is noted visually. Uncoated lensestypically instantly break upon removal from DI water and are assigned aWBUT of 0 seconds. Lenses exhibiting WBUT 5 seconds are consideredwettable and are expected to exhibit adequate wettability (ability tosupport the tear film) on-eye.

Coating Intactness Tests. The intactness of a coating on the surface ofa contact lens can be tested according to Sudan Black stain test asfollow. Contact lenses with a coating (an LbL coating, a plasma coating,or any other coatings) are dipped into a Sudan Black dye solution (SudanBlack in vitamin E oil). Sudan Black dye is hydrophobic and has a greattendency to be adsorbed by a hydrophobic material or onto a hydrophobiclens surface or hydrophobic spots on a partially coated surface of ahydrophobic lens (e.g., silicone hydrogel contact lens). If the coatingon a hydrophobic lens is intact, no staining spots should be observed onor in the lens. All of the lenses under test are fully hydrated.

Tests of coating durability. The lenses are digitally rubbed (wearingdisposable powder-free latex gloves) with Solo-care® multi-purpose lenscare solution for 30 times and then rinsed with saline. The aboveprocedure is repeated for a given times, e.g., from 1 to 30 times,(i.e., number of consecutive digital rubbing tests which imitatecleaning and soaking cycles). The lenses are then subjected to SudanBlack test (i.e., coating intactness test described above) to examinewhether the coating is still intact. To survive digital rubbing test,there is no significantly increased staining spots (e.g., staining spotscovering no more than about 5% of the total lens surface). Water contactangles are measured to determine the coating durability.

Tests of Lenses with Contact Lens Analyzer at low pH (Low pH CLAN). LowpH CLAN tests for the coating coverage on lens surfaces using ahydrophobic (Nile red, also known as Nile Blue Oxazone) dye. Any exposedhydrophobic areas on the lens will bind hydrophobic dye. If ahomogeneous coating on the lens is intact, no staining spots should beobserved on or in the lens. The test is done by dipping a contact lensinto 1N HCl(aq) for about 30 seconds, followed by a 2 second dip in aNile red solution (1-propanol/n-Heptane), and finally a 30 second dip inDI water to rinse off the excess dye. The lens is then placed in theCLAN (digital camera at a fixed focus through a magnifying optics andfilter) where the lens is then illuminated with the blue fluorescenceexcitation light. The image is captured and analyzed by image processingsoftware for the hydrophobic fluorescence dye adsorbed by thehydrophobic surfaces. The lens is considered a failure if the sum ofhalf the number of light pixels and half the number of dark pixels isgreater than 5000.

Bead Testing. Bead testing is used to determine the negative charge onthe contact lens surface. A bead testing value of 50 or less isacceptable for the charge on the lens surface. Higher values alsoreflect if the packaged coating is not able to cover a PAA/PMAA coatedlens which generally has bead numbers≧200. In this method, 0.2 g ofDovex 1×4 chloride form 50-100 mesh (CAS 69011-19-4) is measured in acentrifuge cup followed by addition of 4 ml PBS (phosphate bufferedsaline). A lens is placed on the back side of the tube and the tube isshaken for 1 min at 300 rpm. After this, the tube is rinsed and replacedwith 5 ml of PBS followed by shaking for 1 min at 300 rpm to get rid ofany superficial beads. The lens is than analyzed under a microscope andbeads are counted.

TBO Assay. Prepare a stock solution of sodium phosphate dibasic (0.2%wt/wt, pH 2). Prepare a stock solution of sodium bicarbonate (0.2%wt/wt, pH 10). Prepare a stock solution of Toluidine Blue O (abbreviatedTBO, 2000 ppm) in water. Set two digital block heaters to 35 and 50° C.Prepare freshly diluted 0.1% (wt/wt) solutions of both the pH 2 and pH10 buffers. Prepare 50 ppm TBO solution from the TBO stock solution(2000 ppm). Rinse each lens to be tested in 100 mL of DI water for about5 minutes. Blot each lens to remove excess water using Alpha wipesynthetic wipers. Place the lenses in a 24-well TCPS plate (one lens perwell). Pipette in 1.5 ml of the 50 ppm stain solution into each well andplace the plate on the heating block at 50° C. for 30 minutes. After theabove staining step is complete, remove the lenses and place them in newwells of a 24-well TCPS plate. Pipette in fresh 1.5 ml of 0.1% pH 10buffer solution and the leave the lenses at room temperature for 5 min.After the above rinse step is complete, remove the lenses and place themin new wells of a 24-well TCPS plate. Pipette in fresh 1.5 ml of 0.1% pH10 buffer solution. Leave the plate on the block heater set at 35° C.for 30 min. Remove the lenses from the wells and gently blot away theexcess stain using the Alpha wipe synthetic wipers. Place the lensesinto wells of a new 24-well TCPS plate and pipette in 1.5 ml of 0.1% pH2 solution. Leave the plate on the block heater set at 50° C. for 30min. The bound dye is released from the lenses during this step. Removethe lens from the well. The solutions will be used for UV-VIS analysisand quantification. Prepare calibration standards of 0 to 100 ppm of TBOin 0.1% pH 2 solution. Measure the spectrum of the standard TBOsolutions, the unknown solutions from the coated lenses, and thesolutions from an uncoated lens at wavelengths 625, 630, and 635.Substract the absorbance values from the uncoated lens solutions fromthe coated lens solutions then use the calibration curve to determinethe amount of TBO.

PHMB Method. Prepare 1 liter of phosphate buffered saline (PBS) bydissolving 7.85 g NaCl, 0.773 g monobasic sodium phosphate, and 4.759 gdibasic sodium phosphate in purified water. Adjust pH to 7.1 to 7.3 asneeded. Prepare ATS solution by combining 4.500 grams NaCl, 0.074 gcalcium chloride dihydrate, 0.550 g citric acid monohydrate, 1.400 gsodium citrate, and 493.475 g purified water. Adjust to pH 7.0. Prepare10 ppm PHMB solution in PBS. Place each lens into 3 mL of the 10 ppmPHMB solution overnight (>16 hours). Remove lenses then blot to removeexcess PBS solution. Place 2 blotted lenses into 2 mL of ATS solution.Agitate using an orbital shaker at 250 rpm for 2 hours. After 2 hourscarefully remove the lenses from solution to minimize solution loss.Prepare PHMB standard solutions in PBS (0.5, 1, 2, 4, 8, and 10 ppm).Using a 1 cm quartz cell, measure the absorbance at 240 nm for thestandard, uptake and release samples to determine the concentration ofPHMB.

EXAMPLE 2 Synthesis of Diethyl Azetidinium Methacrylate Ester ChlorideSalt (AZM) Monomer

2a. Synthesis of diethyl hydroxyl azetidinium chloride. Diethyl amine(50 g, 0.686 mole) is dissolved in 25 mL of dry acetonitrile underargon. The solution is cooled down in an ice bath to 0° C. To thissolution, epichlorohydrin (63.248 g, 0.684 mole) in 20 mL of dryacetonitrile is added. After the mixture is stirred at 0° C. for about 5hours, the reaction is then performed at room temperature for anotherabout 27 hours. The solid product is collected by filtration and washedwith cold acetonitrile for a couple times. The typical yield is in therange from 30-50%.

2b: Synthesis of diethyl azetidinium methacrylate ester chloride salt(AZM). In a Schlenk flask equipped with nitrogen flow, the obtainedhydroxy azetidinium chloride salt (60 g, 0.362 mole) is dissolved in 336mL of dry acetonitrile. To this solution, methacrylic acid anhydride(45.73 g, 0.297 mole) and di-tert-butyl-4-methylphenol (7 mg) are addedover about 5 minutes at room temperature. The reaction mixture is thenstirred at room temperature for about 18 hours. The acetonitrile isevaporated and the residual is suspended in 1 L of acetonitrle/diethylether (1:1) solvent mixture. The solid product is collected byfiltration and dried. The typical yield is around 55%

EXAMPLE 3 Synthesis of In-Package Coating (IPC) Copolymers

3a. Preparation of AZM/APMA/PEG/DMA containing copolymer for IPC. In a500 mL glass reaction kettle, 5.0 grams of a solution of methoxypolyethylene glycol 2000 methacrylate (PEG2000-MA) (50% in water), 1.0gram of aminopropylmethacrylamide (APMA), 1.0 gram of AZM prepared inExample 2, 5.47 grams of N,N′-dimethylacrylamide (DMA), and 3.00 mL ofIrgacure 2959 solution (1% in water) are dissolved in 184.53 grams of33.75 mM citrate buffer (pH 4). A lid is put onto the reaction kettlethat contains at least 4 ground glass joints. One used for a glass stirshaft, one for a thermocouple, one for a nitrogen inlet, and one forsampling access. The solution is sparged with nitrogen for 20 minutes atabout 200 mL/min. The nitrogen flow rate is reduced to about 150 mL/min.The stir speed is set to 150 rpm. The reaction kettle is put into aRayonet UV reactor with RPR-3500 UV bulbs. Four UV bulbs are turned onfor about 1 hour at an intensity of about 2.0 mW/cm². After about onehour, the solution is vacuum filtered through qualitative filter paper.The copolymer solution is then purified using 50 kDa dialysis membranesagainst water for 24 hours using a water flow rate of about 40 mL/min.The solids content is determined and diluted to 2% if necessary.

3b. Preparation of AZM/APMA/Acrylamide containing copolymer for IPC. Ina 500 mL glass reaction kettle, 1.5 grams of aminopropylmethacrylamide(APMA), 1.5 grams of AZM prepared in Example 2, 6.97 grams ofacrylamide, and 3.00 mL of Irgacure 2959 solution (1% in water) aredissolved in 187.03 grams of 33.75 mM citrate buffer (pH 4). A lid isput onto the reaction kettle that contains at least 4 ground glassjoints, one used for a glass stir shaft, one for a thermocouple, one fora nitrogen inlet, and one for sampling access. The solution is spargedwith nitrogen for 20 minutes at about 200 mL/min. The nitrogen flow rateis reduced to about 150 mL/min. The stir speed is set to 150 rpm. Thereaction kettle is put into a Rayonet UV reactor with RPR-3500 UV bulbs.Four UV bulbs are turned on for 1 hour at an intensity of about 2.0mW/cm². After 1 hour, the solution is vacuum filtered throughqualitative filter paper. The copolymer solution is then purified using50 kDa dialysis membranes against water for 24 hours using a flow rateof about 40 mL/min. The solids content is determined and diluted to 2%if necessary.

3c. Preparation of AZM/APMA/PEG/AGA containing copolymer for IPC. In a500 mL glass reaction kettle, 5.0 grams of a 50% PEG2000-MA solution inwater, 1.0 grams of aminopropylmethacrylamide (APMA), 1.0 grams of AZMprepared in Example 2, 5.47 grams of acryloyl glucosamine (AGA), and3.00 mL of a 1% Irgacure 2959 solution in water are dissolved in 184.53grams of 33.75 mM citrate buffer (pH 4). A lid is put onto the reactionkettle that contains at least 4 ground glass joints, one used for aglass stir shaft, one for a thermocouple, one for a nitrogen inlet, andone for sampling access. The solution is sparged with nitrogen for 20minutes at about 200 mL/min. The nitrogen flow rate is reduced to about150 mL/min. The stir speed is set to 150 rpm. The reaction kettle is putinto a Rayonet UV reactor with RPR-3500 UV bulbs. Four UV bulbs areturned on for 1 hour at an intensity of about 2.0 mW/cm². After aboutone hour, the solution is vacuum filtered through qualitative filterpaper. The copolymer solution is then purified using 50 kDa dialysismembranes against water for 24 hours. The solids content is determinedand diluted to 2% if necessary.

3d. Preparation of AZM/APMA/AA/Acrylamide containing copolymers for IPC.In a 500 mL glass reaction kettle, 1.5 grams ofaminopropylmethacrylamide (APMA), 1.5 grams of AZM prepared in Example2, 0.2 grams of acrylic acid, 6.77 grams of acrylamide, and 3.00 mL of a1% Irgacure 2959 solution in water are dissolved in 187.03 grams of33.75 mM citrate buffer (pH 4). A lid is put onto the reaction kettlethat contains at least 4 ground glass joints, one used for a glass stirshaft, one for a thermocouple, one for a nitrogen inlet, and one forsampling access. The solution is sparged with nitrogen for 20 minutes atabout 200 mL/min. The nitrogen flow rate is reduced to about 150 mL/min.The stir speed is set to 150 rpm. The reaction kettle is put into aRayonet UV reactor with RPR-3500 UV bulbs. Four UV bulbs are turned onfor about one hour at an intensity of about 2.0 mW/cm². After about onehour, the solution is vacuum filtered through qualitative filter paper.The copolymer solution is then purified using 50 kDa dialysis membranesagainst water for 24 hours using a flow rate of about 40 mL/min. Thesolids content is determined and diluted to 2% if necessary.

EXAMPLE 4 Synthesis of Amphiphilic Copolymers (ACP)

4a. Preparation of AZM/AA/PDMS/DMA containing copolymers. In a 1 L glassreaction kettle 6.0 grams of monomethacryloxypropyl terminatedpolydimethylsiloxane (Gelest catalog# MCR-M11) (PDMS₁₀₀₀-MA) is added. Alid is put onto the reaction kettle that contains at 4 ground glassjoints, one used for a glass stir shaft, one for a thermocouple, one forvacuum and nitrogen inlet, one for a 200 mL pressure equalizing additionfunnel, and one for sampling access. A 2 mbar vacuum is pulled to degasthe PDMS₁₀₀₀-MA for 10 minutes. After about 10 minutes, reaction kettleis filled with nitrogen. This degassing and nitrogen-filing procedure isrepeated 6 times. In the 200 mL pressure equalizing addition funnel, 3.0grams of AZM prepared in Example 2, 6.0 grams of acrylic acid (AA),14.91 grams of DMA, and 3.00 mL of a 1% Irgacure 2959 solution in t-amylalcohol are dissolved in 100.3 grams of t-amyl alcohol and 33.3 grams ofmethanol. A 100 mbar vacuum is pulled on the solution in the additionfunnel for about 10 minutes. After about 10 minutes the funnel is filledwith nitrogen. This degassing and nitrogen-filling procedure is repeated3 times. After both PDMS₁₀₀₀-MA and solution have been degassed, add thesolution to the kettle with the PDMS₁₀₀₀-MA. The stir speed is set to150 rpm. The reaction kettle is put into a Rayonet UV reactor withRPR-3500 UV bulbs. Two UV bulbs are turned on for about one hour at anintensity of about 2.0 mW/cm². The copolymer solution is then purifiedusing 25 kDa dialysis membranes against 1-PrOH for about 35 hoursincluding two changes of 1-PrOH (1-propanol) during that time. Thesolids content is determined and diluted to 10% if necessary.

4b. Preparation of AZM/AA/bulky TRIS/DMA containing copolymer. Theprocedure is the same as 4a except 6.0 grams of bulky TRIS (Gelestcatalog# MCT-M11) is used instead of PDMS₁₀₀₀-MA.

4c. Preparation of AZM/AA/POSS-MA/DMA containing copolymer. In a 1 Lglass reaction kettle 6.0 grams of methacryllsobutyl POSS® (HybridPlastics catalog# MA0702, CAS#307531-94-8) (hereinafter “POSS-MA), 3.0grams of AZM prepared in Example 2, 6.0 grams of acrylic acid (AA),14.91 grams of DMA, 3.00 mL of a 1% Irgacure 2959 solution in t-amylalcohol, 100.3 grams of t-amyl alcohol, and 33.5 g of methanol areadded. The solution is sparged with nitrogen for 20 minutes at about 200mL/min. The nitrogen flow rate is reduced to about 150 mL/min. The stirspeed is set to 150 rpm. The reaction kettle is put into a Rayonet UVreactor with RPR-3500 UV bulbs. Two UV bulbs are turned on for 45minutes. The copolymer solution is then purified using 25 kDa dialysismembranes against 1-PrOH for about 35 hours. The solids content isdetermined and diluted to 10% if necessary.

4d. Preparation of AZM/AA/TRIS/DMA or containing copolymer. Theprocedure is the same as 4c except 6.0 grams of TRIS is used instead ofor 6.0 grams of POSS-MA.

4e. Preparation of AZM/AA/PDMS/DMA containing copolymers. In a 1 L glassreaction kettle 3.0 grams of monomethacryloxypropyl terminatedpolydimethylsiloxane (Gelest catalog# MCR-M11) (PDMS₁₀₀₀-MA) is added. Alid is put onto the reaction kettle that contains at 4 ground glassjoints, one used for a glass stir shaft, one for a thermocouple, one forvacuum and nitrogen inlet, one for a 200 mL pressure equalizing additionfunnel, and one for sampling access. A 2 mbar vacuum is pulled to degasthe PDMS₁₀₀₀-MA for 10 minutes. After about 10 minutes, reaction kettleis filled with nitrogen. This degassing and nitrogen-filing procedure isrepeated 6 times. In the 200 mL pressure equalizing addition funnel, 3.0grams of AZM prepared in Example 2, 12.0 grams of acrylic acid (AA),11.91 grams of DMA, and 3.00 mL of a 1% Irgacure 2959 solution in t-amylalcohol are dissolved in 67 grams of t-amyl alcohol and 67 grams ofmethanol. A 175 mbar vacuum is pulled on the solution in the additionfunnel for about 10 minutes. After about 10 minutes the funnel is filledwith nitrogen. This degassing and nitrogen-filling procedure is repeated3 times. After both PDMS₁₀₀₀-MA and solution have been degassed, add thesolution to the kettle with the PDMS₁₀₀₀-MA. The stir speed is set to150 rpm. The reaction kettle is put into a Rayonet UV reactor withRPR-3500 UV bulbs. Two UV bulbs are turned on for about one hour at anintensity of about 2.0 mW/cm². The copolymer solution is then purifiedusing 25 kDa dialysis membranes against 1-PrOH for about 35 hoursincluding two changes of 1-PrOH (1-propanol) during that time. Thesolids content is determined and diluted to 10% if necessary.

EXAMPLE 5

Preparation of phosphate/citrate buffer concentrate. The bufferconcentrate is prepared by dissolving 0.484% by weight of sodium citratedihydrate, 0.708% by weight of sodium phosphate dibasic, 0.088% byweight of sodium phosphate monobasic, monohydrate, and 1.486% by weightof sodium chloride in DI water. The pH is adjusted to about 7.2, ifnecessary.

Preparation of IPC saline solutions with AZM-containing copolymers.In-package coating solutions (IPC-5A to IPC-5D) are prepared from 2%AZM-containing copolymer solutions (3a-3d of Example 3) and the bufferconcentrate prepared above and have the compositions shown in the tablebelow. The pH of IPC-5A to IPC-5D is adjusted, if necessary, to pH 7.2to 7.4.

IPC AZM-containing Copolymer PBS Water Saline ID Concentration Example #concentrate (g) (g) 5A 1% (w/w) 3a (9 grams) 9 — 5B 1% (w/w) 3b (9grams) 9 — 5C  1% (w/w)1 3c (9 grams) 9 — 5D 0.5% (w/w)    3d (4.5grams) 9 4.5

Preparation of IPC-5E. Poly(AAm-co-AA)(90/10) partial sodium salt (˜90%solid content, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received. Polyamidonamine epichlorohydrin(PAE) (Kymene, an azetidinium content of 0.46 assayed with NMR) ispurchased from Ashland as an aqueous solution and used as received.IPC-5E is prepared by dissolving about 0.07% w/w ofpoly(AAm-co-AA)(90/10) and about 0.15% of PAE (an initial azetidiniummillimolar equivalents of about 8.8 millimole) in phosphate-bufferedsaline (PBS) (about 0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w %Na₂HPO₄.2H₂O, about 0.79 w/w % NaCl) and adjusting the pH to 7.2˜7.4.Then the IPC-5E is heat pre-treated for about 6 hours at about 60° C.(heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) andPAE are partially crosslinked to each other (i.e., not consuming allazetidinium groups of PAE) to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups within the branched polymer network in the IPC-5E.After the heat pre-treatment, the IPC-5E is cooled to room temperaturethen filtered using a 0.22 micron PES membrane filter.

EXAMPLE 6

Silicone hydrogel contact lenses with a PAA coating thereon are preparedaccording to the procedures (the lens formulation, molds, cast-moldingconditions, lens extraction, PAA coating solution, PAA coatingprocedures, etc.) described in Example 19 of U.S. patent applicationpublication No. 2012/0026458 A1 (herein incorporated by reference in itsentirety).

PAA-coating solution. A polyacrylic acid (PAA) coating solution isprepared by dissolving an amount of PAA (M.W.: 450 kDa, from Lubrizol)in a given volume of 1-propanol (1-PrOH) to have a concentration ofabout 0.44% by weight and the pH is adjusted with formic acid to about2.0.

Contact lenses with a PAA coating thereon are packaged in polypropylenelens packaging shells/blisters (one lens per shell) each containing 0.55mL of one of the following packaging salines: phosphate-buffered saline(PBS) and IPC-5A to IPC-5D (prepared in Example 5). The blisters arethen sealed with foil and autoclaved for about 30 minutes at 121° C.Crosslinked coatings are formed during the autoclave on those lensesimmersed in a packaging saline containing an azetidinium-containingcopolymer or polymeric material. Resultant lenses after autoclave arecharacterized and the results are reported in the table below.

PBS IPC-5A IPC-5B IPC-5C IPC-5D WBUT (s) 10+ 9 10 1 14 Lubricity 0 0.50.5 0.5 0.5 Bead Test >250    2 121 42 117 Low pH CLAN Pass Pass PassPass Pass

EXAMPLE 7

Preparation of Lenses. Silicone hydrogel contact lenses are prepared bycast-molding according the procedures (the lens formulation, molds,cast-molding conditions, etc.) described in Example 19 of U.S. patentapplication publication No. 2012/0026458 A1 (herein incorporated byreference in its entirety).

PMAA-coating solutions. A polymethacrylic acid (PMAA) solution isprepared by dissolving PMAA (Mn˜418K) and formic acid in a given volumeof a water/1-propanol mixture, and then diluted with water and1-propanol to forming PMAA coating solutions having the followingcompositions:

-   -   1. 40×PMAA: PMAA (0.011% w/w); 1-propanol (86.19% w/w); water        (9.63% w/w); and formic acid (3.74% w/w).    -   2. FS PMAA: PMAA (0.44% w/w); 1-propanol (86.63% w/w); water        (9.63% w/w); and formic acid (3.74% w/w).

PMAA-coated lenses. Cast-molded contact lenses obtained as above areextracted and coated by dipping in the following series of baths: DIwater bath for about 56 seconds; 3 methyl ethyl ketone (MEK) baths forabout 22, 78, 226 second respectively; one DI water bath for about 56seconds; one bath of PMAA coating solution (prepared above) for about100 seconds; one bath of a water/1-propanol 50%/50% mixture for about 56seconds; one bath of water for about 56 seconds; one bath of phosphatebuffered saline for about 56 seconds; and one DI water bath for about 56seconds.

Application of crosslinked coating. Contact lenses with a PMAA coatingthereon are packaged in polypropylene lens packaging shells/blisters(one lens per shell) each containing 0.55 mL of one of the followingpackaging salines: PBS (as control), IPC-5A (prepared in Example 5), andIPC-5B (prepared in Example 5). The blisters are then sealed with foiland autoclaved for about 30 minutes at about 121° C. Crosslinkedcoatings are formed during the autoclave on those lenses immersed in apackaging saline containing an azetidinium-containing copolymer orpolymeric material.

Characterization of SiHy lenses. Resultant lenses after autoclave arecharacterized and the results are reported in the table below.

Packaging Saline PBS IPC-5A IPC-5B Contact angle (degrees) 103 46 36WBUT (s) NA 3 6 Lubricity NA 0.5 0.5 NA = data not collected

EXAMPLE 8

This example illustrates preparation of an amphiphilic copolymer (ACP)that uses AZM (as prepared in Example 2) and acrylic acid to provide across-linkable primary coating designed to react with the IPC copolymer.

The structure of such a copolymer is shown below.

AZM is the electrophile and acrylic acid is the nucleophile in thecopolymer. Both can react with a crosslinkable copolymer added to asaline solution to apply a in-package crosslinked coating on a siliconehydrogel contact lens. The copolymer also incorporatespolydimethylsiloxane segment (PDMS) to provide a hydrophobic interactionto attach the copolymer to the surface of a hydrophobic lens (e.g., asilicone hydrogel contact lens). DMA is used to provide hydrophilicityand high molecular weight copolymers. The copolymer has much lessacrylic acid content (concentration) compared to polyacrylic acid (PAA)or polymethacrylic acid (PMAA) homopolymers.

The preferred range of weight percentages of monomers used in a reactionmixture for preparing a copolymer of the invention is listed in table 1below. The copolymer is prepared according to the procedure similar tothat described in Example 4 for preparing Copolymer 4a.

AZM Acrylic Acid PDMS DMA Range 10-15% 10-40% 10-60% Remaining %

Preparation of Lenses. Silicone hydrogel contact lenses are prepared bycast-molding according the procedures (the lens formulation, molds,cast-molding conditions, etc.) described in Example 19 of U.S. patentapplication publication No. 2012/0026458 A1 (herein incorporated byreference in its entirety).

Preparation of ACP coating solutions. Amphiphilic copolymer solutions(herein after ACP coating solutions I to IV) each are prepared bydissolving one of ACP copolymers 4a to 4e (about 10% solution) preparedin Example 4 in a mixture of 1-propanol (85%) and water (15%). The ACPconcentration is about 1% by weight.

ACP-coated lenses. Cast-molded contact lenses as above are extracted andcoated with ACP by dipping in the following series of baths: one DIwater bath for about 56 seconds; 3 MEK baths for about 22, 78, and 224second respectively; one DI water bath for about 56 seconds; one bath ofACP coating solution (about 1% by weight) in a mixture of1-propanol/water (85%/15%) for about 180 seconds; one bath of awater/1-propanol (58%/42%) mixture for about 180 seconds; one bath of awater/1-propanol (72%/28%) mixture for about 180 seconds; and one DIwater bath for about 180 seconds. ACP-I coated lenses are obtained usingACP coating solution I (containing ACP copolymer 4a); ACP-II coatedlenses are obtained using ACP coating solution II (containing ACPcopolymer 4b); ACP-III coated lenses are obtained using ACP coatingsolution II (containing ACP copolymer 4c); ACP-IV coated lenses areobtained using ACP coating solution IV (containing ACP copolymer 4d).Control A lenses are obtained according to the procedures above, exceptthat bath 6 is free of ACP and contains only the solvent mixture.

Application of crosslinked coating. ACP-coated contact lenses preparedabove are packaged in polypropylene lens packaging shells/blisters (onelens per shell) each containing 0.55 mL of one of the followingpackaging salines: PBS (as control) and IPC-5E (prepared in Example 5).Control A lenses are packaged in polypropylene lens packagingshells/blisters (one lens per shell) each containing 0.55 mL of PBS.Control B lenses are ACP-coated lenses which are packaged inpolypropylene lens packaging shells/blisters (one lens per shell) eachcontaining 0.55 mL of PBS. The blisters are then sealed with foil andautoclaved for 30 minutes at about 121° C. Crosslinked coatings areformed during the autoclave on those lenses immersed in a packagingsaline containing an azetidinium-containing copolymer or polymericmaterial.

Characterization of SiHy lenses. Resultant lenses after autoclave arecharacterized and the results are reported in the table below.

Control A Control B Test Co- none ACP4a-4d ACP 4a ACP 4b ACP 4c ACP 4dpolymer Packaging IPC-5E PBS IPC-5E Saline Contact 104 103-110 64 63 7666 angle (°) WBUT (s) 1 1-2 2 1 1 3 Lubricity 3.5 3 2 2 2.5 3 Low pHFail Fail Pass Pass Pass Pass CLAN

EXAMPLE 9

Preparation of Lenses. Silicone hydrogel contact lenses with a PAAcoating thereon are prepared according to the procedures (the lensformulation, molds, cast-molding conditions, lens extraction, PAAcoating solution, PAA coating procedures, etc.) described in Example 19of U.S. patent application publication No. 2012/0026458 A1 (hereinincorporated by reference in its entirety).

Preparation of AZM/APMA/DMA containing copolymer. In a 500 mL glassreaction kettle, 1.0 gram of aminopropylmethacrylamide (APMA), 2.5 gramsof AZM prepared in Example 2, 6.47 grams of N,N′-dimethylacrylamide(DMA), and 3.00 mL of Irgacure 2959 solution (1% in water) are dissolvedin 187.0 grams of 33.75 mM citrate buffer (pH 4). A lid is put onto thereaction kettle that contains at least 4 ground glass joints. One usedfor a glass stir shaft, one for a thermocouple, one for a nitrogeninlet, and one for sampling access. The solution is sparged withnitrogen for 20 minutes at about 200 mL/min. The nitrogen flow rate isreduced to about 150 mL/min. The stir speed is set to 150 rpm. Thereaction kettle is put into a Rayonet UV reactor with RPR-3500 UV bulbs.Four UV bulbs are turned on for about 1 hour at an intensity of about2.0 mW/cm². After about one hour, the solution is vacuum filteredthrough qualitative filter paper. The copolymer solution is thenpurified using 50 kDa dialysis membranes against water for 24 hoursusing a water flow rate of about 40 mL/min. The solids content isdetermined and diluted to 2% if necessary.

Preparation of IPC saline using AZM/APMA/DMA co-polymer. IPC 9A isprepared by making a 0.5% w/w solution of the AZM/APMA/DMA copolymerprepared above. A 2% copolymer solution is diluted by the PBSconcentrate in Example 5 (50% w/w) and water (25% w/w) to get the finalconcentration of 0.5 w/w % Poly(AAm-co-AA)(90/10) partial sodium salt(90% solid content, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received. IPC 9B is prepared bydissolving about 0.1% w/w of poly(AAm-co-AA)(90/10) and about 0.5% w/wof the AZM/APMA/DMA copolymer. IPC 9C is prepared by dissolving about0.3% w/w of poly(AAm-co-AA)(90/10) and about 0.5% w/w of theAZM/APMA/DMA copolymer. Both IPC 9B and 9C are adjusted to pH 7.2-7.4 byadding about 0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w % Na₂HPO₄.2H₂O andabout 0.79 w/w % NaCl. After that, IPC 9B and 9C are pre-heated for 10hours at 70° C. During this heat pretreatment, poly(AAm-co-AA) and AZMcopolymer are partially reacted to each other (i.e., not consuming allazetidinium groups of the copolymer) to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups within the branched polymer network in the IPC 9B and9C. After the heat pre-treatment, the IPC is filtered using a 0.22micron PES membrane filter.

Application of the cross-linked coating. PAA coated lenses are packagedin polypropylene shells (one lens per shell) containing 0.65 ml ofeither IPC 9A, 9B or 9C. Blisters are sealed and autoclaved for 45 minat 121° C.

Characterization of the lenses. Tests are done on the lenses todetermine the efficacy of the coating salines. As can be seen, thecopolymer of AZM/APMA/DMA itself is not capable of providing goodlubricity on the lenses but addition of poly (AAm-co-AA) improves thelubricity tremendously.

Packaging Saline IPC 9A IPC 9B IPC 9C WBUT (s) 9 8-10 10-11 Lubricity 40.5 0 Low pH CLAN Pass Pass Pass Bead Testing Pass (2) Pass (2) Pass (0)

EXAMPLE 10

Preparation of Lenses. Silicone hydrogel contact lenses with a PAAcoating thereon are prepared according to the procedures (the lensformulation, molds, cast-molding conditions, lens extraction, PAAcoating solution, PAA coating procedures, etc.) described in Example 19of U.S. patent application publication No. 2012/0026458 A1 (hereinincorporated by reference in its entirety).

Preparation of Copolymers of Methacrylic acid, Acrylic acid, and AZM. Ina 500 mL glass reaction kettle, methacrylic acid (MAA), acrylic acid(AA), 158 grams of 25% sodium citrate dehydrate solution in water, AZMprepared in Example 2, and 2.65 mL of Irgacure 2959 solution (1% inwater) are added. The pH is adjusted to 5.5 using 5N NaOH. Water isadded up to 265 grams. A lid is put onto the reaction kettle thatcontains at least 4 ground glass joints. One used for a glass stirshaft, one for a thermocouple, one for a nitrogen inlet, and one forsampling access. The solution is sparged with nitrogen for 20 minutes atabout 200 mL/min. The nitrogen flow rate is reduced to about 150 mL/min.The stir speed is set to 150 rpm. The reaction kettle is put into aRayonet UV reactor with RPR-3500 UV bulbs. Two UV bulbs are turned onfor about 1 hour at an intensity of about 2.0 mW/cm². After about onehour, the solution is vacuum filtered through qualitative filter paper.The copolymer solution is then purified by ultrafiltration using a 10kDa membranes until the solution conductivity reaches less than 10uS/cm. The solids content is determined and diluted to 0.8% ifnecessary. Various copolymers are prepared with the ratios given in thetable below.

10A 10B 10C 10D 10E MAA (g) 26.5 21.2 18.5 23.85 23.85 AA (g) — 5.3 5.3— 1.33 AZM (g) — — 2.65 g 2.65 1.33 5N NaOH (mL) 39 43 37.5 35 41 DIwater (g) 38.9 37.4 40.4 40.7 38.0

EXAMPLE 11

Preparation of Lenses. Silicone hydrogel contact lenses are prepared bycast-molding according the procedures (the lens formulation, molds,cast-molding conditions, etc.) described in Example 19 of U.S. patentapplication publication No. 2012/0026458 A1 (herein incorporated byreference in its entirety).

PMAA copolymer coating solution. Polymethacrylic acid (PMAA) copolymercoating solutions are prepared from PMAA copolymers prepared in Example10 to have the following composition: PMAA copolymer (0.011% w/w) whichis one of PMAA 10A to 10E prepared in Example 10; 1-propanol (86.63%w/w); water (9.63% w/w); and formic acid (3.74% w/w).

PMAA copolymer coated lenses. Cast-molded contact lenses obtained asabove are extracted and coated by dipping in the following series ofbaths: DI water bath for about 56 seconds; 3 methyl ethyl ketone (MEK)baths for about 22, 78, 226 second respectively; one DI water bath forabout 56 seconds; one bath of PMAA copolymer coating solution (preparedabove) for about 100 seconds; one bath of a water/1-propanol 50%/50%mixture for about 56 seconds; one bath of water for about 56 seconds;one bath of phosphate buffered saline for about 56 seconds; and one DIwater bath for about 56 seconds. The lenses are immediately tested foracid group content by TBO Assay as described in Example 1. The data areshown below.

10A 10B 10C 10D 10E TBO Assay 12.4 +/− 1.0 29.9 +/− 1.1 5.0 +/− 2.6 4.9+/− 1.5 7.1 +/− 1.0 (nanomoles/lens)

EXAMPLE 12

13.0 g methacrylic acid and 1.2 mg mercaptoethanol are dissolved in243.0 g water and the pH adjusted to 3.0 by adding aqueous sodiumhydroxide solution (33%). The solution is purged for 1 hour gently withnitrogen under stirring in a round flask. The solution is heated to 90°C. after degassing. 3.6 mg2,2′-Azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (VA-086, Wako) areseparately dissolved in 5 mL water, purged with nitrogen for 1 hour,filled into a syringe and added to the synthesis solution to start thepolymerization. The synthesis is carried out for 20 hours under stirringat 90° C. After the polymerization the pH of the synthesis solution isadjusted to pH=3 by adding sulfuric acid and the PMAA is purified byaqueous ultrafiltration with 10 kDa cellulose membranes (12× solventexchange). PMAA is finally dried by freeze drying.

EXAMPLE 13

15.0 g methacrylic acid and 3.4 mg mercaptoethanol are dissolved in285.0 g water and the pH adjusted to 3.5 by adding aqueous sodiumhydroxide solution (33%). The solution is purged gently for 1 hour withnitrogen under stirring in a round flask. The solution is heated to 50°C. after degassing. 9.1 mg 2,2′-Azobis[2-(2-imidazolin-2-yl)propane](VA-061, Wako) are separately dissolved in 5 mL water, gently purgedwith nitrogen for 1 hour, filled into a syringe and added to thesynthesis solution to start the polymerization. The synthesis is carriedout for 20 hours under stirring at 50° C. After the polymerization thepH of the synthesis solution is adjusted to pH=3 by adding sulfuric acidand the PMAA is purified by aqueous ultrafiltration with 10 kDacellulose membranes (12× solvent exchange). PMAA is finally dried byfreeze drying.

EXAMPLE 14

Various lenses (Purevision® from Bausch & Lamb; ACUVUE® 2® from Johnson& Johnson; SiHy lenses with FS PMAA/IPC-5A coating thereon as preparedin Example 7; SiHy lenses with 40×PMAA/IPC-5A coating thereon asprepared in Example 7; SiHy lenses with ACP-4-e/IPC-5A coating thereonas prepared according to the procedures described in Example 8 and byusing ACP-4-e prepared in Example 4 as the prime coating and IPC salineIPC-5A prepared in Example 5 in forming the crosslinked coating) aretested for polyhexamethylene biguanide (PHMB) uptake and releaseaccording to the procedures described in Example 1. The results of thetests are shown in FIG. 1. The PHMB uptake is least for lenses having anACP prime coating.

What is claimed is:
 1. An azetidinium-containing vinylic monomer, beingrepresented by formula (2)

in which: R″ is hydrogen or methyl; p1, p2, and p3 independent of oneanother are zero or 1; Y₄ is a linkage selected from the groupconsisting of a direct bond, —O—, —NR′—, —C(O)—NR′—, —NR′—C(O)—,—O—C(O)—NH—, —NH—C(O)—O—, —NR′—C(O)—NH—, —NH—C(O)NR′—, —C(O)—O—,—O—C(O)—, R′ is hydrogen, a C₁-C₂₀ unsubstituted or substituted, linearor branched alkyl group; Z₄, is a direct bond, a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkylene divalent radical optionallycontaining therein one or more linkages of —O—, —NR′—, and —C(O)—, aC₁-C₇ alkyleneoxy C₁-C₇ alkylene divalent radical, or a divalent radicalof —(CH(R″)CH₂O)_(r1)—CH(R″)CH₂— in which R″ is as defined above and r1is an integer of 1 to 20; and Z₅ is a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkyl group,—(CH₂)_(r2)—O—(CH₂CH₂O)_(r1)—Z₆ in which r1 is as defined above, r2 iszero or an integer of 1 to 7, and Z₆ is a C₁-C₅ alkyl.
 2. Theazetidinium-containing vinylic monomer of claim 1, wherein theazetidinium-containing vinylic monomer is obtained by reactingepichlorohydrin directly with a vinylic monomer having a secondary aminegroup.
 3. The azetidinium-containing vinylic monomer of claim 2, whereinthe vinylic monomer having a secondary amine group is N-allyl C₁-C₁₂alkanamine.
 4. The azetidinium-containing vinylic monomer of claim 3,wherein the N-allyl C₁-C₁₂ alkanamine is N-ethyl-2-methylallylamine,N-ethylallylamine, N-allylmethylamine, N-allyl-1-pentanamine,N-allyl-2-methyl-1-pentanamine, N-Allyl-2,3-dimethyl-1-pentanamine,N-allyl-1-hexanamine, N-allyl-2-methyl-1-hexanamine,N-allyl-1-heptanamine, N-allyl-1-octanamine, N-allyl-1-ecanamine, orN-allyl-1-dodecanamine.
 5. The azetidinium-containing vinylic monomer ofclaim 2, wherein the vinylic monomer having a secondary amine group isobtained by reacting an epoxy compound having one sole epoxy group withallylamine, vinylamine, amino-C₂-C₆ alkyl (meth)acrylate, or amino-C₂-C₆alkyl (meth)acrylamide.
 6. The azetidinium-containing vinylic monomer ofclaim 5, wherein the epoxy compound is 1,2-epoxy C₃-C₁₂ alkanes.
 7. Theazetidinium-containing vinylic monomer of claim 5, wherein the epoxycompound is a mono-epoxy terminated polyethyleneglycol.
 8. Theazetidinium-containing vinylic monomer of claim 2, wherein the vinylicmonomer having a secondary amine group is obtained by reacting aC₁-C₁₂alkanamine or amino-C₂-C₁₂ alkanol with an epoxy-containingvinylic monomer.
 9. The azetidinium-containing vinylic monomer of claim8, wherein the epoxy-containing vinylic monomer is glycidyl(meth)acrylate, vinyl glycidyl ether, or allyl glycidyl ether.